The first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages

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In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was a breakthrough in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another. https://www.youtube.com/embed/cisOFfBPZk0?wmode=transparent&start=0 The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.

Champions of xenotransplantation regard it as the solution to organ shortages across the world. In December 2023, 1,445 people in Australia were on the waiting list for donor kidneys. In the United States, more than 89,000 are waiting for kidneys.

One biotech CEO says gene-edited pigs promise “an unlimited supply of transplantable organs”.

Not, everyone, though, is convinced transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.

There are two critical barriers to the procedure’s success: organ rejection and the transmission of animal viruses to recipients.

But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.

What is CRISPR?

CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery allows them to integrate and ultimately destroy viral DNA by cutting it.

In 2012, two teams of scientists discovered how to harness this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins.

When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could program the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site.

In 2020, the two scientists leading these teams were awarded a Nobel prize for their work.

In the case of the latest xenotransplantation, CRISPR technology was used to edit 69 genes in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes. https://www.youtube.com/embed/UKbrwPL3wXE?wmode=transparent&start=0 How does CRISPR work?

A busy time for gene-edited xenotransplantation

While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.

In 2022 and 2023, two patients with terminal heart diseases, who were ineligible for traditional heart transplants, were granted regulatory permission to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures.

Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a clinically dead man (with family consent). The liver functioned well up until the ten-day limit of the trial.

How is this latest example different?

The gene-edited pig kidney was transplanted into a relatively young, living, legally competent and consenting adult.

The total number of gene edits edits made to the donor pig is very high. The researchers report making 69 edits to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.

Clearly, the race to transform these organs into viable products for transplantation is ramping up.

From biotech dream to clinical reality

Only a few months ago, CRISPR gene editing made its debut in mainstream medicine.

In November, drug regulators in the United Kingdom and US approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease.

The treatment, known as Casgevy, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the unhealthy gene that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape.

Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.

Sickle cells have a different shape to healthy round red blood cells
CRISPR technology is aiming to restore diseased red blood cells to their healthy round shape. Sebastian Kaulitzki/Shutterstock

We’ll be talking more about gene-editing

Medicine and gene technology regulators are increasingly asked to approve new experimental trials using gene editing and CRISPR.

However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.

For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to early-stage embryonic cells in vitro (in the lab).

In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying 15 years’ imprisonment.

No jurisdiction in the world has laws that expressly permits heritable human genome editing. However, some countries lack specific regulations about the procedure.

Is this the future?

Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.

For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting beyond seven months.

While authorisation for this recent US transplant has been granted under the so-called “compassionate use” exemption, conventional clinical trials of pig-human xenotransplantation have yet to commence.

But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval in the US or elsewhere.

By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem some way off.

Christopher Rudge, Law lecturer, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • Brain Maker – by Dr. David Perlmutter

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Regular 10almonds readers probably know about the gut-brain connection already, so what’s new here?

    Dr. David Perlmutter takes us on a tour of gut and brain health, specifically, the neuroprotective effect of healthy gut microbiota.

    This seems unlikely! After all, vagus nerve or no, the gut microbiota are confined to the gut, and the brain is kept behind the blood-brain barrier. So how does one thing protect the other?

    Dr. Perlmutter presents the relevant science, and the honest answer is, we’re not 100% sure how this happens! We do know part of it: that bad gut microbiota can result in a “leaky gut”, and that may in turn lead to such a thing as a “leaky brain”, where the blood-brain barrier has been compromised and some bad things can get in with the blood.

    When it comes to gut-brain health…

    Not only is the correlation very strong, but also, in tests where someone’s gut microbiota underwent a radical change, e.g. due to…

    • antibiotics (bad)
    • fasting (good)
    • or a change in diet (either way)

    …their brain health changed accordingly—something we can’t easily check outside of a lab, but was pretty clear in those tests.

    We’re also treated to an exposé on the links between gut health, brain health, inflammation, and dementia… Which links are extensive.

    In closing, we’ll mention that throughout this book we’re also given many tips and advices to improve our gut/brain health, reverse damage done already, and set ourselves up well for the future.

    Click here to check out “Brain Maker” on Amazon and take care of this important part of your health!

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  • 5 Steps To Quit Sugar Easily

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Sugar is one of the least healthy things that most people consume, yet because it’s so prevalent, it can also be tricky to avoid at first, and the cravings can also be a challenge. So, how to quit it?

    Step by step

    Dr. Mike Hansen recommends the following steps:

    • Be aware: a lot of sugar consumption is without realizing it or thinking about it, because of how common it is for there to be added sugar in things we might purchase ready-made, even supposedly healthy things like yogurts, or easy-to-disregard things like condiments.
    • Recognize sugar addiction: a controversial topic, but Dr. Hansen comes down squarely on the side of “yes, it’s an addiction”. He wants us to understand more about the mechanics of how this happens, and what it does to us.
    • Reduce gradually: instead of going “cold turkey”, he recommends we avoid withdrawal symptoms by first cutting back on liquid sugars like sodas, juices, and syrups, before eliminating solid sugar-heavy things like candy, sugar cookies, etc, and finally the more insidious “why did they put sugar in this?” added-sugar products.
    • Find healthy alternatives: simple like-for-like substitutions; whole fruits instead of juices/smoothies, for example. 10almonds tip: stuffing dates with an almond each makes it very much like eating chocolate, experientially!
    • Manage cravings: Dr. Hansen recommends distraction, and focusing on upping other healthy habits such as hydration, exercise, and getting more vegetables.

    For more on each of these, enjoy:

    Click Here If The Embedded Video Doesn’t Load Automatically!

    Want to learn more?

    You might also like to read:

    Take care!

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  • Reishi Mushrooms: Which Benefits Do They Really Have?

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    Reishi Mushrooms

    Another Monday Research Review, another mushroom! If we keep this up, we’ll have to rename it “Mushroom Monday”.

    But, there’s so much room for things to say, and these are fun guys to write about, as we check the science for any spore’ious claims…

    Why do people take reishi?

    Popular health claims for the reishi mushroom include:

    • Immune health
    • Cardiovascular health
    • Protection against cancer
    • Antioxidant qualities
    • Reduced fatigue and anxiety

    And does the science agree?

    Let’s take a look, claim by claim:

    Immune health

    A lot of research for this has been in vitro (ie, with cell cultures in labs), but promising, for example:

    Immunomodulating Effect of Ganoderma lucidum (Lingzhi) and Possible Mechanism

    (that is the botanical name for reishi, and the Chinese name for it, by the way)

    That’s not to say there are no human studies though; here it was found to boost T-cell production in stressed athletes:

    Effect of Ganoderma lucidum capsules on T lymphocyte subsets in football players on “living high-training low”

    Cardiovascular health

    Here we found a stack of evidence for statistically insignificant improvements in assorted measures of cardiovascular health, and some studies where reishi did not outperform placebo.

    Because the studies were really not that compelling, instead of taking up room (and your time) with them, we’re going to move onto more compelling, exciting science, such as…

    Protection against cancer

    There’s a lot of high quality research for this, and a lot of good results. The body of evidence here is so large that even back as far as 2005, the question was no longer “does it work” or even “how does it work”, but rather “we need more clinical studies to find the best doses”. Researchers even added:

    ❝At present, lingzhi is a health food supplement to support cancer patients, yet the evidence supporting the potential of direct in vivo anticancer effects should not be underestimated.❞

    ~ Yuen et al.

    Check it out:

    Anticancer effects of Ganoderma lucidum: a review of scientific evidence

    Just so you know we’re not kidding about the weight of evidence, let’s drop a few extra sources:

    By the way, we shortened most of those titles for brevity, but almost all of the continued with “by” followed by a one-liner of how it does it.

    So it’s not a “mysterious action” thing, it’s a “this is a very potent medicine and we know how it works” thing.

    Antioxidant qualities

    Here we literally only found studies to say no change was found, one that found a slight increase of antioxidant levels in urine. It’s worth noting that levels of a given thing (or its metabolites, in the case of some things) in urine are often quite unhelpful regards knowing what’s going on in the body, because we get to measure only what the body lost, not what it gained/kept.

    So again, let’s press on:

    Reduced fatigue and anxiety

    Most of the studies for this that we could find pertained to health-related quality of life for cancer patients specifically, so (while they universally give glowing reports of reishi’s benefits to health and happiness of cancer patients), that’s a confounding factor when it comes to isolating its effects on reduction of fatigue and anxiety in people without cancer.

    Here’s one that looked at it in the case of reduction of fatigue, anxiety, and other factors, in patients without cancer (but with neurathenia), in which they found it was “significantly superior to placebo with respect to the clinical improvement of symptoms”.

    Summary:

    • Reishi mushroom’s anti-cancer properties are very, very clear
    • There is also good science to back immune health claims
    • It also has been found to significantly reduce fatigue and anxiety in unwell patients (we’d love to see more studies on its benefits in otherwise healthy people, though)

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  • Can I Eat That? – by Jenefer Roberts

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    The answer to the question in the title is: you can eat pretty much anything, if you’re prepared for the consequences!

    This book looks to give you the information to make your own decisions in that regard. There’s a large section on the science of glucose metabolism in the context of food (other aspects of glucose metabolism aren’t covered), so you will not simply be told “raw carrots are good; mashed potatoes are bad”, you’ll understand many factors that affect it, e.g:

    • Macronutrient profiles of food and resultant base glycemic indices
    • How the glycemic index changes if you cut something, crush it, mash it, juice it, etc
    • How the glycemic index changes if you chill something, heat it, fry it, boil it, etc
    • The many “this food works differently in the presence of this other food” factors
    • How your relative level of insulin resistance affects things itself

    …and much more.

    The style is simple and explanatory, without deep science, but with good science and comprehensive advice.

    There are also the promised recipes; they’re in an appendix at the back and aren’t the main meat of the book, though.

    Bottom line: if you’ve ever found it confusing working out what works how in the mysterious world of diabetes nutrition, this book is a top tier demystifier.

    Click here to check out Can I Eat That?, and gain confidence in your food choices!

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  • What Are “Adaptogens” Anyway? (And Other Questions Answered)

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    It’s Q&A Day at 10almonds!

    Have a question or a request? You can always hit “reply” to any of our emails, or use the feedback widget at the bottom!

    In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!

    As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!

    So, no question/request too big or small

    ❝I tried to use your calculator for heart health, and was unable to enter in my height or weight. Is there another way to calculate? Why will that field not populate?❞

    (this is in reference to yesterday’s main feature “How Are You, Really? And How Old Is Your Heart?“)

    How strange! We tested it in several desktop browsers and several mobile browsers, and were unable to find any version that didn’t work. That includes switching between metric and imperial units, per preference; both appear to work fine. Do be aware that it’ll only take numerical imput, though.

    Did anyone else have this problem? Let us know! (You can reply to this email, or use the handy feedback widget at the bototm)

    ❝I may have missed it, but how much black pepper provides benefits?❞

    So, for any new subscribers joining us today, this is about two recent main features:

    As for a daily dosage of black pepper, it varies depending on the benefit you’re looking for, but:

    • 5–20mg of piperine is the dosage range used in most scientific studies we looked at
    • 10mg is a very common dosage found in many popular supplements
    • That’s the mass of piperine though, so if taking it as actual black pepper rather than as an extract, ½ teaspoon is considered sufficient to enjoy benefits.

    ❝I loved the health benefits of pepper. I do not like pepper. Where can I get it as a supplement?❞

    You can simply buy whole black peppercorns and take a few with water as though they were tablets. Your stomach acid will do the rest. Black pepper is also good for digestion, so taking it with a meal is best.

    You can buy piperine (black pepper extract) by itself as a supplement in powder form, but if you don’t like black pepper, you will probably not like this powder either. We couldn’t find it readily in capsule form.

    You can buy piperine (black pepper extract) as an adjunct to other supplements, with perhaps the most common/popular being turmeric capsules that also contain 10mg (or more) piperine per capsule. Shop around if you like, but here’s one that has 15mg piperine* per capsule, for example.

    *They call it “Bioperine®” but that is literally just piperine. Same goes if you see “Absorbagen™”, it’s still just piperine.

    ❝What do you mean when you say that something is adaptogenic?❞

    Simple version: it means it helps the body adapt to stress, by adjusting the body’s natural responses. Thus, adaptogenic supplements can be contrasted with tranquilizing drugs that mask stress by brute force, for example.

    Technical version: adaptogenic activity refers to improving physiological stress resilience, such as by moderating and modulating hypothalamic–pituitary–adrenal axis signaling, and/or by regulating levels of endogenic compounds involved in the cellular stress response.

    Read more (technical version):

    Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity

    Read more (simple version):

    European Medicines Agency’s Reflection Paper On The Adaptogenic Concept

    Enjoy!

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  • Prolonged Grief: A New Mental Disorder?

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    The issue is not whether certain mental conditions are real—they are. It is how we conceptualize them and what we think treating them requires.

    The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) features a new diagnosis: prolonged grief disorder—used for those who, a year after a loss, still remain incapacitated by it. This addition follows more than a decade of debate. Supporters argued that the addition enables clinicians to provide much-needed help to those afflicted by what one might simply consider a too much of grief, whereas opponents insisted that one mustn’t unduly pathologize grief and reject an increasingly medicalized approach to a condition that they considered part of a normal process of dealing with loss—a process which in some simply takes longer than in others.    

    By including a condition in a professional classification system, we collectively recognize it as real. Recognizing hitherto unnamed conditions can help remove certain kinds of disadvantages. Miranda Fricker emphasizes this in her discussion of what she dubs hermeneutic injustice: a specific sort of epistemic injustice that affects persons in their capacity as knowers1. Creating terms like ‘post-natal depression’ and ‘sexual harassment’, Fricker argues, filled lacunae in the collectively available hermeneutic resources that existed where names for distinctive kinds of social experience should have been. The absence of such resources, Fricker holds, put those who suffered from such experiences at an epistemic disadvantage: they lacked the words to talk about them, understand them, and articulate how they were wronged. Simultaneously, such absences prevented wrong-doers from properly understanding and facing the harm they were inflicting—e.g. those who would ridicule or scold mothers of newborns for not being happier or those who would either actively engage in sexual harassment or (knowingly or not) support the societal structures that helped make it seem as if it was something women just had to put up with. 

    For Fricker, the hermeneutical disadvantage faced by those who suffer from an as-of-yet ill-understood and largely undiagnosed medical condition is not an epistemic injustice. Those so disadvantaged are not excluded from full participation in hermeneutic practices, or at least not through mechanisms of social coercion that arise due to some structural identity prejudice. They are not, in other words, hermeneutically marginalized, which for Fricker, is an essential characteristic of epistemic injustice. Instead, their situation is simply one of “circumstantial epistemic bad luck”2. Still, Fricker, too, can agree that providing labels for ill-understood conditions is valuable. Naming a condition helps raise awareness of it, makes it discursively available and, thus, a possible object of knowledge and understanding. This, in turn, can enable those afflicted by it to understand their experience and give those who care about them another way of nudging them into seeking help. 

    Surely, if adding prolonged grief disorder to the DSM-5 were merely a matter of recognizing the condition and of facilitating assistance, nobody should have any qualms with it. However, the addition also turns intense grief into a mental disorder—something for whose treatment insurance companies can be billed. With this, significant forces of interest enter the scene. The DSM-5, recall, is mainly consulted by psychiatrists. In contrast to talk-therapists like psychotherapists or psychoanalysts, psychiatrists constitute a highly medicalized profession, in which symptoms—clustered together as syndromes or disorders—are frequently taken to require drugs to treat them. Adding prolonged grief disorder thus heralds the advent of research into various drug-based grief therapies. Ellen Barry of the New York Times confirms this: “naltrexone, a drug used to help treat addiction,” she reports, “is currently in clinical trials as a form of grief therapy”, and we are likely to see a “competition for approval of medicines by the Food and Drug Administration.”3

    Adding diagnoses to the DSM-5 creates financial incentives for players in the pharmaceutical industry to develop drugs advertised as providing relief to those so diagnosed. Surely, for various conditions, providing drug-induced relief from severe symptoms is useful, even necessary to enable patients to return to normal levels of functioning. But while drugs may help suppress feelings associated with intense grief, they cannot remove the grief. If all mental illnesses were brain diseases, they might be removed by adhering to some drug regimen or other. Note, however, that ‘mental illness’ is a metaphor that carries the implicit suggestion that just like physical illnesses, mental afflictions, too, are curable by providing the right kind of physical treatment. Unsurprisingly, this metaphor is embraced by those who stand to massively benefit from what profits they may reap from selling a plethora of drugs to those diagnosed with any of what seems like an ever-increasing number of mental disorders. But metaphors have limits. Lou Marinoff, a proponent of philosophical counselling, puts the point aptly:

    Those who are dysfunctional by reason of physical illness entirely beyond their control—such as manic-depressives—are helped by medication. For handling that kind of problem, make your first stop a psychiatrist’s office. But if your problem is about identity or values or ethics, your worst bet is to let someone reify a mental illness and write a prescription. There is no pill that will make you find yourself, achieve your goals, or do the right thing.

    Much more could be said about the differences between psychotherapy, psychiatry, and the newcomer in the field: philosophical counselling. Interested readers may benefit from consulting Marinoff’s work. Written in a provocative, sometimes alarmist style, it is both entertaining and—if taken with a substantial grain of salt—frequently insightful. My own view is this: from Fricker’s work, we can extract reasons to side with the proponents of adding prolonged grief disorder to the DSM-5. Creating hermeneutic resources that allow us to help raise awareness, promote understanding, and facilitate assistance is commendable. If the addition achieves that, we should welcome it. And yet, one may indeed worry that practitioners are too eager to move from the recognition of a mental condition to the implementation of therapeutic interventions that are based on the assumption that such afflictions must be understood on the model of physical disease. The issue is not whether certain mental conditions are real—they are. It is how we conceptualize them and what we think treating them requires.

    No doubt, grief manifests physically. It is, however, not primarily a physical condition—let alone a brain disease. Grief is a distinctive mental condition. Apart from bouts of sadness, its symptoms typically include the loss of orientation or a sense of meaning. To overcome grief, we must come to terms with who we are or can be without the loved one’s physical presence in our life. We may need to reinvent ourselves, figure out how to be better again and whence to derive a new purpose. What is at stake is our sense of identity, our self-worth, and, ultimately, our happiness. Thinking that such issues are best addressed by popping pills puts us on a dangerous path, leading perhaps towards the kind of dystopian society Aldous Huxley imagined in his 1932 novel Brave New World. It does little to help us understand, let alone address, the moral and broader philosophical issues that trouble the bereaved and that lie at the root not just of prolonged grief but, arguably, of many so-called mental illnesses.

    Footnotes:

    1 For this and the following, cf. Fricker 2007, chapter 7.

    2 Fricker 2007: 152

    3 Barry 2022

    References:

    Barry, E. (2022). “How Long Should It Take to Grieve? Psychiatry Has Come Up With an Answer.” The New York Times, 03/18/2022, URL = https://www.nytimes.com/2022/03/18/health/prolonged-grief-
    disorder.html [last access: 04/05/2022])
    Fricker, M. (2007). Epistemic Injustice. Power & the Ethics of knowing. Oxford/New York: Oxford University Press.
    Huxley, A. (1932). Brave New World. New York: Harper Brothers.
    Marinoff, L. (1999). Plato, not Prozac! New York: HarperCollins Publishers.

    Professor Raja Rosenhagen is currently serving as Assistant Professor of Philosophy, Head of Department, and Associate Dean of Academic Affairs at Ashoka University. He earned his PhD in Philosophy from the University of Pittsburgh and has a broad range of philosophical interests (see here). He wrote this article a) because he was invited to do so and b) because he is currently nurturing a growing interest in philosophical counselling.

    This article is republished from OpenAxis under a Creative Commons license. Read the original article.

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