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.

Bushfires are currently burning in Australian states including Victoria, Tasmania, Western Australia and South Australia. In some areas, fire authorities have warned residents about the presence of smoke.

Bushfire smoke is harmful to our health. Tiny particles of ash can lodge deep in the lungs.

Exposure to this type of smoke may worsen existing conditions such as asthma, and induce a range of health effects from irritation of the eyes, nose and throat to changes in the cardiovascular system.

Public health recommendations during smoke events tend to provide general advice, and don’t often include advice specifically geared at children. But children are not just little adults. They are uniquely vulnerable to environmental hazards such as bushfire smoke for a number of reasons.

Different physiology, different behaviour

Children’s lungs are still developing and maturing.

Airways are smaller in children, especially young children, which is associated with greater rates of particle deposition – when particles settle on the surfaces of the airways.

Children also breathe more air per kilogram of body weight compared with adults, and therefore inhale more polluted air relative to their size.

Further, children’s detoxification systems are still developing, so environmental toxins take longer to effectively clear from their bodies.

Meanwhile, children’s behaviour and habits may expose them to more environmental toxins than adults. For example, they tend to do more physical activity and spend more time outdoors. Higher levels of physical activity lead to more air inhaled per kilogram of body weight.

Also, a normal and important part of children’s early play is exploring their environment, including by putting things in their mouth. This can result in kids ingesting soil, dust and dirt, which often contain environmental contaminants.

For these reasons, it’s important to consider the specific needs of children when providing advice on what to do when there’s smoke in the air.

Keeping our environments healthy

The Australian government offers recommendations for minimising the health risks from exposure to bushfire smoke. The main advice includes staying indoors and keeping doors and windows closed.

This is great advice when the smoke is thick outside, but air pollutants may still accumulate inside the home. So it’s important to air your home once the smoke outside starts to clear. Take advantage of wind changes to open up and get air moving out of the house with a cross breeze.

Kids are natural scientists, so get them involved. For example, you and your child can “rate” the air each hour by looking at a landmark outside your home and rating how clearly you can see it. When you notice the haze is reducing, open up the house and clear the air.

Because air pollutants settle onto surfaces in our home and into household dust, an easy way to protect kids during smoky periods is to do a daily dust with a wet cloth and vacuum regularly. This will remove pollutants and reduce ingestion by children as they play. Frequent hand washing helps too.

Healthy bodies and minds

Research exploring the effects of bushfire smoke exposure on children’s health is sparse. However, during smoke events, we do see an increase in hospital visits for asthma, as well as children reporting irritation to their eyes, nose and throat.

If your child has asthma or another medical condition, ensure they take any prescribed medications on a regular schedule to keep their condition well controlled. This will minimise the risk of a sudden worsening of their symptoms with bushfire smoke exposure.

Make sure any action plans for symptom flare-ups are up to date, and ensure you have an adequate supply of in-date medication somewhere easy to locate and access.

Kids can get worried during bushfires, and fire emergencies have been linked with a reduction in children’s mental health. Stories such as the Birdie’s Tree books can help children understand these events do pass and people help one another in times of difficulty.

Learning more about air pollution can help too. Our group has a children’s story explaining how air pollution affects our bodies and what can help.

It’s also important for parents and caregivers not to get too stressed, as children cope better when their parents manage their own anxiety and help their children do the same. Try to strike a balance between being vigilant and staying calm.

What about masks?

N95 masks can protect the wearer from fine particles in bushfire smoke, but their use is a bit complicated when it comes to kids. Most young children won’t be able to fit properly into an N95 mask, or won’t tolerate the tight fit for long periods. Also, their smaller airways make it harder for young children to breathe through a mask.

If you choose to use an N95 mask for your children, it’s best to save them for instances when high-level outdoor exposure is unavoidable, such as if you’re going outside when the smoke is very thick.

N95 masks should be replaced after around four hours or when they become damp.

If your child has an existing heart or lung condition, consult their doctor before having them wear an N95 mask.

Our team is currently recruiting for a study exploring the effects of bushfire smoke in children. If you live in south east Queensland and are interested in participating in the event of a bushfire or hazard reduction burn near your home, please express your interest here.

Dwan Vilcins, Group leader, Environmental Epidemiology, Children’s Health Environment Program, The University of Queensland; Nicholas Osborne, Associate Professor, School of Public Health, The University of Queensland, and Paul D. Robinson, Conjoint Professor in Respiratory and Sleep Medicine, Child Health Research Centre, The University of Queensland

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