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.

Corporations have used feminist language to promote their products for decades. In the 1980s, companies co-opted messaging about female autonomy to encourage women’s consumption of unhealthy commodities, such as tobacco and alcohol.

Today, feminist narratives around empowerment and women’s rights are being co-opted to market interventions that are not backed by evidence across many areas of women’s health. This includes by commercial companies, industry, mass media and well-intentioned advocacy groups.

Some of these health technologies, tests and treatments are useful in certain situations and can be very beneficial to some women.

However, promoting them to a large group of asymptomatic healthy women that are unlikely to benefit, or without being transparent about the limitations, runs the risk of causing more harm than good. This includes inappropriate medicalisation, overdiagnosis and overtreatment.

In our analysis published today in the BMJ, we examine this phenomenon in two current examples: the anti-mullerian hormone (AMH) test and breast density notification.

The AMH test

The AMH test is a blood test associated with the number of eggs in a woman’s ovaries and is sometimes referred to as the “egg timer” test.

Although often used in fertility treatment, the AMH test cannot reliably predict the likelihood of pregnancy, timing to pregnancy or specific age of menopause. The American College of Obstetricians and Gynaecologists therefore strongly discourages testing for women not seeking fertility treatment.

Despite this, several fertility clinics and online companies market the AMH test to women not even trying to get pregnant. Some use feminist rhetoric promising empowerment, selling the test as a way to gain personalised insights into your fertility. For example, “you deserve to know your reproductive potential”, “be proactive about your fertility” and “knowing your numbers will empower you to make the best decisions when family planning”.

The use of feminist marketing makes these companies appear socially progressive and champions of female health. But they are selling a test that has no proven benefit outside of IVF and cannot inform women about their current or future fertility.

Our recent study found around 30% of women having an AMH test in Australia may be having it for these reasons.

Misleading women to believe that the test can reliably predict fertility can create a false sense of security about delaying pregnancy. It can also create unnecessary anxiety, pressure to freeze eggs, conceive earlier than desired, or start fertility treatment when it may not be needed.

While some companies mention the test’s limitations if you read on, they are glossed over and contradicted by the calls to be proactive and messages of empowerment.

Breast density notification

Breast density is one of several independent risk factors for breast cancer. It’s also harder to see cancer on a mammogram image of breasts with high amounts of dense tissue than breasts with a greater proportion of fatty tissue.

While estimates vary, approximately 25–50% of women in the breast screening population have dense breasts.

Stemming from valid concerns about the increased risk of cancer, advocacy efforts have used feminist language around women’s right to know such as “women need to know the truth” and “women can handle the truth” to argue for widespread breast density notification.

However, this simplistic messaging overlooks that this is a complex issue and that more data is still needed on whether the benefits of notifying and providing additional screening or tests to women with dense breasts outweigh the harms.

Additional tests (ultrasound or MRI) are now being recommended for women with dense breasts as they have the ability to detect more cancer. Yet, there is no or little mention of the lack of robust evidence showing that it prevents breast cancer deaths. These extra tests also have out-of-pocket costs and high rates of false-positive results.

Large international advocacy groups are also sponsored by companies that will financially benefit from women being notified.

While stronger patient autonomy is vital, campaigning for breast density notification without stating the limitations or unclear evidence of benefit may go against the empowerment being sought.

Ensuring feminism isn’t hijacked

Increased awareness and advocacy in women’s health are key to overcoming sex inequalities in health care.

But we need to ensure the goals of feminist health advocacy aren’t undermined through commercially driven use of feminist language pushing care that isn’t based on evidence. This includes more transparency about the risks and uncertainties of health technologies, tests and treatments and greater scrutiny of conflicts of interests.

Health professionals and governments must also ensure that easily understood, balanced information based on high quality scientific evidence is available. This will enable women to make more informed decisions about their health.

Brooke Nickel, NHMRC Emerging Leader Research Fellow, University of Sydney and Tessa Copp, NHMRC Emerging Leader Research Fellow, University of Sydney

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