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.

It’s one of the most pervasive messages about technology and sleep. We’re told bright, blue light from screens prevents us falling asleep easily. We’re told to avoid scrolling on our phones before bedtime or while in bed. We’re sold glasses to help filter out blue light. We put our phones on “night mode” to minimise exposure to blue light.

But what does the science actually tell us about the impact of bright, blue light and sleep? When our group of sleep experts from Sweden, Australia and Israel compared scientific studies that directly tested this, we found the overall impact was close to meaningless. Sleep was disrupted, on average, by less than three minutes.

We showed the message that blue light from screens stops you from falling asleep is essentially a myth, albeit a very convincing one.

Instead, we found a more nuanced picture about technology and sleep.

What we did

We gathered evidence from 73 independent studies with a total of 113,370 participants of all ages examining various factors that connect technology use and sleep.

We did indeed find a link between technology use and sleep, but not necessarily what you’d think.

We found that sometimes technology use can lead to poor sleep and sometimes poor sleep can lead to more technology use. In other words, the relationship between technology and sleep is complex and can go both ways.

How is technology supposed to harm sleep?

Technology is proposed to harm our sleep in a number of ways. But here’s what we found when we looked at the evidence:

• bright screen light – across 11 experimental studies, people who used a bright screen emitting blue light before bedtime fell asleep an average of only 2.7 minutes later. In some studies, people slept better after using a bright screen. When we were invited to write about this evidence further, we showed there is still no meaningful impact of bright screen light on other sleep characteristics including the total amount or quality of sleep
• arousal is a measure of whether people become more alert depending on what they’re doing on their device. Across seven studies, people who engaged in more alerting or “exciting” content (for example, video games) lost an average of only about 3.5 minutes of sleep compared to those who engaged in something less exciting (for example, TV). This tells us the content of technology alone doesn’t affect sleep as much as we think
• we found sleep disruption at night (for example, being awoken by text messages) and sleep displacement (using technology past the time that we could be sleeping) can lead to sleep loss. So while technology use was linked to less sleep in these instances, this was unrelated to being exposed to bright, blue light from screens before bedtime.

Which factors encourage more technology use?

Research we reviewed suggests people tend to use more technology at bedtime for two main reasons:

• to “fill the time” when they’re not yet sleepy. This is common for teenagers, who have a biological shift in their sleep patterns that leads to later sleep times, independent of technology use.
• to calm down negative emotions and thoughts at bedtime, for apparent stress reduction and to provide comfort.

There are also a few things that might make people more vulnerable to using technology late into the night and losing sleep.

We found people who are risk-takers or who lose track of time easily may turn off devices later and sacrifice sleep. Fear of missing out and social pressures can also encourage young people in particular to stay up later on technology.

What helps us use technology sensibly?

Last of all, we looked at protective factors, ones that can help people use technology more sensibly before bed.

The two main things we found that helped were self-control, which helps resist the short-term rewards of clicking and scrolling, and having a parent or loved one to help set bedtimes.

Why do we blame blue light?

The blue light theory involves melatonin, a hormone that regulates sleep. During the day, we are exposed to bright, natural light that contains a high amount of blue light. This bright, blue light activates certain cells at the back of our eyes, which send signals to our brain that it’s time to be alert. But as light decreases at night, our brain starts to produce melatonin, making us feel sleepy.

It’s logical to think that artificial light from devices could interfere with the production of melatonin and so affect our sleep. But studies show it would require light levels of about 1,000-2,000 lux (a measure of the intensity of light) to have a significant impact.

Device screens emit only about 80-100 lux. At the other end of the scale, natural sunlight on a sunny day provides about 100,000 lux.

What’s the take-home message?

We know that bright light does affect sleep and alertness. However our research indicates the light from devices such as smartphones and laptops is nowhere near bright or blue enough to disrupt sleep.

There are many factors that can affect sleep, and bright, blue screen light likely isn’t one of them.

The take-home message is to understand your own sleep needs and how technology affects you. Maybe reading an e-book or scrolling on socials is fine for you, or maybe you’re too often putting the phone down way too late. Listen to your body and when you feel sleepy, turn off your device.

Chelsea Reynolds, Casual Academic/Clinical Educator and Clinical Psychologist, College of Education, Psychology and Social Work, Flinders University

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