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.

Parents are often faced with well-meaning opinions and conflicting advice about what to feed their babies.

The latest guidance from the World Health Organization (WHO) recommends formula-fed babies can switch to cow’s milk from six months. Australian advice says parents should wait until 12 months. No wonder some parents, and the health professionals who advise them, are confused.

So what do parents need to know about the latest advice? And when is cow’s milk an option?

What’s the updated advice?

Last year, the WHO updated its global feeding guideline for children under two years old. This included recommending babies who are partially or totally formula fed can have whole animal milks (for example, full-fat cow’s milk) from six months.

This recommendation was made after a systematic review of research by WHO comparing the growth, health and development of babies fed infant formula from six months of age with those fed pasteurised or boiled animal milks.

The review found no evidence the growth and development of babies who were fed infant formula was any better than that of babies fed whole, fresh animal milks.

The review did find an increase in iron deficiency anaemia in babies fed fresh animal milk. However, WHO noted this could be prevented by giving babies iron-rich solid foods daily from six months.

On the strength of the available evidence, the WHO recommended babies fed infant formula, alone or in addition to breastmilk, can be fed animal milk or infant formula from six months of age.

The WHO said that animal milks fed to infants could include pasteurised full-fat fresh milk, reconstituted evaporated milk, fermented milk or yoghurt. But this should not include flavoured or sweetened milk, condensed milk or skim milk.

Why is this controversial?

Australian government guidelines recommend “cow’s milk should not be given as the main drink to infants under 12 months”. This seems to conflict with the updated WHO advice. However, WHO’s advice is targeted at governments and health authorities rather than directly at parents.

The Australian dietary guidelines are under review and the latest WHO advice is expected to inform that process.

OK, so how about iron?

Iron is an essential nutrient for everyone but it is particularly important for babies as it is vital for growth and brain development. Babies’ bodies usually store enough iron during the final few weeks of pregnancy to last until they are at least six months of age. However, if babies are born early (prematurely), if their umbilical cords are clamped too quickly or their mothers are anaemic during pregnancy, their iron stores may be reduced.

Cow’s milk is not a good source of iron. Most infant formula is made from cow’s milk and so has iron added. Breastmilk is also low in iron but much more of the iron in breastmilk is taken up by babies’ bodies than iron in cow’s milk.

Babies should not rely on milk (including infant formula) to supply iron after six months. So the latest WHO advice emphasises the importance of giving babies iron-rich solid foods from this age. These foods include:

• meat
• eggs
• vegetables, including beans and green leafy vegetables
• pulses, including lentils
• ground seeds and nuts (such as peanut or other nut butters, but with no added salt or sugar).

You may have heard that giving babies whole cow’s milk can cause allergies. In fact, whole cow’s milk is no more likely to cause allergies than infant formula based on cow’s milk.

What are my options?

The latest WHO recommendation that formula-fed babies can switch to cow’s milk from six months could save you money. Infant formula can cost more than five times more than fresh milk (A$2.25-$8.30 a litre versus $1.50 a litre).

For families who continue to use infant formula, it may be reassuring to know that if infant formula becomes hard to get due to a natural disaster or some other supply chain disruption fresh cow’s milk is fine to use from six months.

It is also important to know what has not changed in the latest feeding advice. WHO still recommends infants have only breastmilk for their first six months and then continue breastfeeding for up to two years or more. It is also still the case that infants under six months who are not breastfed or who need extra milk should be fed infant formula. Toddler formula for children over 12 months is not recommended.

All infant formula available in Australia must meet the same standard for nutritional composition and food safety. So, the cheapest infant formula is just as good as the most expensive.

What’s the take-home message?

The bottom line is your baby can safely switch from infant formula to fresh, full-fat cow’s milk from six months as part of a healthy diet with iron-rich foods. Likewise, cow’s milk can also be used to supplement or replace breastfeeding from six months, again alongside iron-rich foods.

If you have questions about introducing solids your GP, child health nurse or dietitian can help. If you need support with breastfeeding or starting solids you can call the National Breastfeeding Helpline (1800 686 268) or a lactation consultant.

Karleen Gribble, Adjunct Associate Professor, School of Nursing and Midwifery, Western Sydney University; Naomi Hull, PhD candidate, food security for infants and young children, University of Sydney, and Nina Jane Chad, Research Fellow, University of Sydney School of Public Health, University of Sydney

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