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.

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.

“I have to be hard on myself,” Sarah told me in a recent telehealth psychology session. “I would never reach my potential if I was kind and let myself off the hook.”

I could empathise with this fear of self-compassion from clients such as Sarah (not her real name). From a young age, we are taught to be kind to others, but self-kindness is never mentioned.

Instead, we are taught success hinges on self-sacrifice. And we need a healthy inner critic to bully us forward into becoming increasingly better versions of ourselves.

But research shows there doesn’t have to be a trade-off between self-compassion and success.

Self-compassion can help you reach your potential, while supporting you to face the inevitable stumbles and setbacks along the way.

What is self-compassion?

Self-compassion has three key ingredients.

1. Self-kindness

This involves treating yourself with the same kindness you would extend towards a good friend – via your thoughts, feelings and actions – especially during life’s difficult moments.

For instance, if you find yourself fixating on a minor mistake you made at work, self-kindness might involve taking a ten-minute walk to shift focus, and reminding yourself it is OK to make mistakes sometimes, before moving on with your day.

2. Mindfulness

In this context, mindfulness involves being aware of your own experience of stress or suffering, rather than repressing or avoiding your feelings, or over-identifying with them.

Basically, you must see your stress with a clear (mindful) perspective before you can respond with kindness. If we avoid or are consumed by our suffering, we lose perspective.

3. Common humanity

Common humanity involves recognising our own experience of suffering as something that unites us as being human.

For instance, a sleep-deprived parent waking up (for the fourth time) to feed their newborn might choose to think about all the other parents around the world doing exactly the same thing – as opposed to feeling isolated and alone.

It’s not about day spas, or booking a manicure

When Sarah voiced her fear that self-compassion would prevent her success, I explained self-compassion is distinct from self-indulgence.

“So is self-compassion just about booking in more mani/pedis?” Sarah asked.

Not really, I explained. A one-off trip to a day spa is unlikely to transform your mental health.

Instead, self-compassion is a flexible psychological resilience factor that shapes our thoughts, feelings and actions.

It’s associated with a suite of benefits to our wellbeing, relationships and health.

What does the science say?

Over the past 20 years, we’ve learned self-compassionate people enjoy a wide range of benefits. They tend to be happier and have fewer psychological symptoms of distress.

Those high on self-compassion persevere following a failure. They say they are more motivated to overcome a personal weakness than those low on self-compassion, who are more likely to give up.

So rather than feeling trapped by your inadequacies, self-compassion encourages a growth mindset, helping you reach your potential.

However, self-compassion is not a panacea. It will not change your life circumstances or somehow make life “easy”. It is based on the premise that life is hard, and provides practical tools to cope.

It’s a factor in healthy ageing

I research menopause and healthy ageing and am especially interested in the value of self-compassion through menopause and in the second half of life.

Because self-compassion becomes important during life’s challenges, it can help people navigate physical symptoms (for instance, menopausal hot flushes), life transitions such as divorce, and promote healthy ageing.

I’ve also teamed up with researchers at Autism Spectrum Australia to explore self-compassion in autistic adults.

We found autistic adults report significantly lower levels of self-compassion than neurotypical adults. So we developed an online self-compassion training program for this at-risk population.

Three tips for self-compassion

You can learn self-compassion with these three exercises.

1. What would you say to a friend?

Think back to the last time you made a mistake. What did you say to yourself?

If you notice you’re treating yourself more like an enemy than a friend, don’t beat yourself up about it. Instead, try to think about what you might tell a friend, and direct that same friendly language towards yourself.

2. Harness the power of touch

Soothing human touch activates the parasympathetic “relaxation” branch of our nervous system and counteracts the fight or flight response.

Specifically, self-soothing touch (for instance, by placing both hands on your heart, stroking your forearm or giving yourself a hug) reduces cortisol responses to psychosocial stress.

3. What do I need right now?

Sometimes, it can be hard to figure out exactly what self-compassion looks like in a given moment. The question “what do I need right now” helps clarify your true needs.

For example, when I was 37 weeks pregnant, I woke up bolt awake one morning at 3am.

Rather than beating myself up about it, or fretting about not getting enough sleep, I gently placed my hands on my heart and took a few deep breaths. By asking myself “what do I need right now?” it became clear that listening to a gentle podcast/meditation fitted the bill (even though I wanted to addictively scroll my phone).

Lydia Brown, Senior Lecturer in Psychology, The University of Melbourne

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