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.

An estimated one in five women and one in 16 men in Australia have experienced sexual violence.

After such a traumatic experience, it’s understandable many are unsure if they want to report it to the police. In fact, less than 10% of Australian women who experience sexual assault ever make a police report.

In Australia there is no time limit on reporting sexual assault to police. However, there are tight time frames for collecting forensic evidence, which can sometimes be an important part of the police investigation, whether it’s commenced at the time or later.

This means the decision of whether or not to undergo a medical forensic examination needs to be made quite quickly after an assault.

I work as a medical forensic examiner. Here’s what you can expect if you present for a medical forensic examination after a sexual assault.

A team of specialists

There are about 100 sexual assault services throughout Australia providing 24-hour care. As with other areas of health care, there are extra challenges in regional and rural areas, where there are often further distances to travel and staff shortages.

Sexual assault services in Australia are free regardless of Medicare status. To find your nearest service you can call 1800 RESPECT (1800 737 732) or Full Stop Australia (1800 385 578) who can also provide immediate telephone counselling support.

It’s important to call the local sexual assault service before turning up. They can provide the victim-survivor with information and advice to prevent delays and make the process as helpful as possible.

The consultation usually occurs in a hospital emergency department which has a designated forensic suite, or in a specialised forensic service.

The victim-survivor is seen by a doctor or nurse trained in medical and forensic care. There’s a sexual assault counsellor, crisis worker or social worker present to support the patient and offer counselling advice. This is called an “integrated response” with medical and psychosocial staff working together.

In most cases the victim-survivor can have their own support person present too.

Depending on what the victim-survivor wants, the doctor or nurse will take a history of the assault to guide any medical care which may be needed (such as emergency contraception) and to guide the examination.

Sexual assault services are always very aware of giving victim-survivors a choice about having a medical forensic examination. If a person presents to a sexual assault service, they can receive counselling and medical care without undergoing a forensic examination if they do not wish to. https://www.youtube.com/embed/CGlbTgia0Ek?wmode=transparent&start=0 Sexual assault services are inclusive of all genders.

Collecting forensic samples

Samples collected during a medical forensic examination can sometimes identify the perpetrator’s DNA or intoxicating substances (alcohol or drugs that might be relevant to the investigation). The window of opportunity to collect these samples can be as short as 12 hours, or up to 5–7 days, depending on the nature of the sexual assault.

In most of Australia, an adult who has experienced a recent sexual assault can be offered a medical forensic examination without making a report to police.

Depending on the state or territory, the forensic samples can usually be stored for 3 to 12 months (up to 100 years in Tasmania). This allows the victim-survivor time to decide if they want to release them to police for processing.

The doctor or nurse will collect the samples using a sexual assault investigation kit, or a “rape kit”.

Collecting these samples might involve taking swabs to try to detect DNA from external and internal genital areas and anywhere there may have been DNA transfer. This can be from skin cells, where the perpetrator touched the victim-survivor, or from bodily fluids including semen or saliva.

The doctor or nurse carrying out the examination do their best to minimise re-traumatisation, by providing the victim-survivor information, choices and control at every step of the process.

How about STIs and pregnancy?

During the consultation, the doctor or nurse will address any concerns about sexually transmitted infections (STIs) and pregnancy, if applicable.

In most cases the risk of STIs is small. But follow-up testing at 1–2 weeks for infections such as chlamydia and gonorrhoea, and at 6–12 weeks for infections such as syphilis and HIV, is usually recommended.

Emergency contraception (sometimes called the “morning after pill”) can be provided to prevent pregnancy. It can be taken up to five days after sexual assault (but the sooner the better) with follow-up pregnancy testing recommended at 2–3 weeks.

Things have improved over time

When I was a junior doctor in the late 90s, taking forensic swabs was usually the responsibility of the busy obstetrics and gynaecology trainee in the emergency department, who was often managing multiple patients and had little training in forensics. There was also usually no supportive counsellor.

Anecdotally, both the doctor and the patient were traumatised by this experience. Research shows that when specialised, integrated services are not provided, victim-survivors’ feelings of powerlessness are magnified.

But the way we carry out medical forensic examinations after sexual assault in Australia has improved over the years.

With patient-centred practices, and designated forensic and counselling staff, the experience for the patient is thought to be empowering rather than re-traumatising.

Our research

In new research published in the Australian Journal of General Practice, my colleagues and I explored the experience of the medical forensic examination from the victim-survivor’s perspective.

We surveyed 291 patients presenting to a sexual assault service in New South Wales (where I work) over four years.

Some 75% of patients reported the examination was reassuring and another 20% reported it was OK. Only 2% reported that it was traumatising. The majority (98%) said they would recommend a friend present to a sexual assault service if they were in a similar situation.

While patients spoke positively about the care they received, many commented that the sexual assault service was not visible enough. They didn’t know how to find it or even that it existed.

We know many victim-survivors don’t present to a sexual assault service or undergo a medical forensic examination after a sexual assault. So we need to do more to increase the visibility of these services.

The National Sexual Assault, Family and Domestic Violence Counselling Line – 1800 RESPECT (1800 737 732) – is available 24 hours a day, seven days a week for any Australian who has experienced, or is at risk of, family and domestic violence and/or sexual assault.

Mary Louise Stewart, Senior Career Medical Officer, Northern Sydney Local Health District; PhD Candidate, University of Sydney

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