The first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages

Massachusetts General Hospital Christopher Rudge, University of Sydney

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.

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.

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.

CRISPR technology is aiming to restore diseased red blood cells to their healthy round shape. Sebastian Kaulitzki/Shutterstock

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.

Read More........→March 29, 2024

What is a sonar pulse and how can it injure humans under water?

An echo sounder on a boat uses sound waves to help gauge the depth of the water. mark_vyz/Shutterstock Christine Erbe, Curtin University

Over the weekend, the Australian government revealed that last Tuesday its navy divers had sustained “minor injuries”, likely due to sonar pulses from a Chinese navy vessel.

The divers had been clearing fishing nets from the propellers of HMAS Toowoomba while in international waters off the coast of Japan. According to a statement from deputy prime minister Richard Marles, despite HMAS Toowoomba communicating with internationally recognised signals, the Chinese vessel approached the Australian ship and turned on its sonar, forcing the Australian divers to exit the water.

The incident prompted a response from the Australian government, who labelled the incident “unsafe and unprofessional”. But what exactly is a sonar pulse, and what kinds of injuries can sonar cause to divers?

What is sonar?

Light doesn’t travel well under water – even in clear waters, you can see perhaps some tens of metres. Sound, however, travels very well and far under water. This is because water is much denser than air, and so can respond faster and better to acoustic pressure waves – sound waves.

Because of these properties, ships use sonar to navigate through the ocean and to “see” under water. The word “sonar” stands for sound navigation and ranging.

Sonar equipment sends out short acoustic (sound) pulses or pings, and then analyses the echoes. Depending on the timing, amplitude, phase and direction of the echoes the equipment receives, you can tell what’s under water – the seafloor, canyon walls, coral, fishes, and of course ships and submarines.

Most vessels – from small, private boats to large commercial tankers – use sonar. However, compared to your off-the-shelf sonar used for finding fish, navy sonars are stronger.

What are the effects of sonar on divers?

This is a difficult topic to study, because you don’t want to deliberately expose humans to harmful levels of sound. There are, however, anecdotes from various navies and accidental exposures. There have also been studies on what humans can hear under water, with or without neoprene suits, hoods, or helmets.

We don’t hear well under water – no surprise, since we’ve evolved to live on land. Having said that, you would hear a sonar sound under water (a mid-to-high pitch noise) and would know you’ve been exposed.

When it comes to naval sonars, human divers have rated the sound as “unpleasant to severe” at levels of roughly 150dB re 1 µPa (decibel relative to a reference pressure of one micropascal, the standard reference for underwater sound). This would be perhaps, very roughly, 10km away from a military sonar. Note that we can’t compare sound exposure under water to what we’d receive through the air, because there are too many physical differences between the two.

Human tolerance limits are roughly 180dB re 1 µPa, which would be around 500m from military sonar. At such levels, humans might experience dizziness, disorientation, temporary memory and concentration impacts, or temporary hearing loss. We don’t have information on what levels the Australian divers were exposed to, but their injuries were described as minor.

At higher received levels, closer ranges, or longer exposures, you might see more severe physiological or health impacts. In extreme cases, in particular for impulsive, sudden sound (which sonar is not), sound can cause damage to tissues and organs.

What does sonar do to marine animals?

Some of the information on what noise might do to humans under water comes from studies and observations of animals.

While they typically don’t have outer ears (except for sea lions), marine mammals have inner ears that function similarly to ours. They can receive hearing damage from noise, just like we do. This might be temporary, like the ringing ears or reduced sensitivity you might experience after a loud concert, or it can be permanent.

Marine mammals living in a dark ocean rely on sound and hearing to a greater extent than your average human. They use sound to navigate, hunt, communicate with each other and to find mates. Toothed whales and dolphins have evolved a biological echo sounder or biosonar, which sends out series of clicks and listens for echoes. So, interfering with their sounds or impacting their hearing can disrupt critical behaviours.

Finally, sound may also impact non-mammalian fauna, such as fishes, which rely on acoustics rather than vision for many of their life functions.

Christine Erbe, Director, Centre for Marine Science & Technology, Curtin University

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

Read More........→November 22, 2023

How consciousness may rely on brain cells acting collectively – new psychedelics research on rats

Psychedelics can help uncover consciousness. agsandrew/Shutterstock Pär Halje, Lund University

Psychedelics are known for inducing altered states of consciousness in humans by fundamentally changing our normal pattern of sensory perception, thought and emotion. Research into the therapeutic potential of psychedelics has increased significantly in the last decade. While this research is important, I have always been more intrigued by the idea that psychedelics can be used as a tool to study the neural basis of human consciousness in laboratory animals. We ultimately share the same basic neural hardware with other mammals, and possibly some basic aspects of consciousness, too. So by examining what happens in the brain when there’s a psychedelically induced change in conscious experience, we can perhaps glean insights into what consciousness is in the first place.We still don’t know a lot about how the networks of cells in the brain enable conscious experience. The dominating view is that consciousness somehow emerges as a collective phenomenon when the dispersed information processing of individual neurons (brain cells) is integrated as the cells interact.But the mechanism by which this is supposed to happen remains unclear. Now our study on rats, published in Communications Biology, suggests that psychedelics radically change the way that neurons interact and behave collectively.Our study compared two different classes of psychedelics in rats: the classic LSD type and the less-typical ketamine type (ketamine is an anaesthetic in larger doses). Both classes are known to induce psychedelic experiences in humans, despite acting on different receptors in the brain. Exploring brain waves: We used electrodes to simultaneously measure electrical activity from 128 separate areas of the brain of nine awake rats while they were given psychedelics. The electrodes could pick up two kinds of signals: electrical brain waves caused by the cumulative activity in thousands of neurons, and smaller transient electrical pulses, called action potentials, from individual neurons. The classic psychedelics, such as LSD and psilocybin (the active ingredient in magic mushrooms), activates a receptor in the brain (5-HT2A) which normally binds to serotonin, a neurotransmitter that regulates mood and many other things. Ketamine, on the other hand, works by inhibiting another receptor (NMDA), which normally is activated by glutamate, the primary neurotransmitter in the brain for making neurons fire. We speculated that, despite these differences, the two classes of psychedelics might have similar effects on the activity of brain cells. Indeed, it turned out that both drug classes induced a very similar and distinctive pattern of brain waves in multiple brain regions. The brain waves were unusually fast, oscillating about 150 times per second. They were also surprisingly synchronised between different brain regions. Short bursts of oscillations at a similar frequency are known to occur occasionally under normal conditions in some brain

Brain waves on electroencephalogram EEG. Chaikom/Shutterstock

regions. But in this case, it occurred for prolonged durations.  First, we assumed that a single brain structure was generating the wave and that it then spread to other locations. But the data was not consistent with that scenario. Instead, we saw that the waves went up and down almost simultaneously in all parts of the brain where we could detect them – a phenomenon called phase synchronisation. Such tight phase synchronisation over such long distances has to our knowledge never been observed before. We were also able to measure action potentials from individual neurons during the psychedelic state. Action potentials are electrical pulses, no longer than a thousandth of a second, that are generated by the opening and closing of ion channels in the cell membrane. The action potentials are the primary way that neurons influence each other. Consequently, they are considered to be the main carrier of information in the brain. However, the action potential activity caused by LSD and ketamine differed significantly. As such, they could not be directly linked to the general psychedelic state. For LSD, neurons were inhibited – meaning they fired fewer action potentials – in all parts of the brain. For ketamine, the effect depended on cell type – certain large neurons were inhibited, while a type of smaller, locally connecting neurons, fired more. Therefore, it is probably the synchronised wave phenomenon – how the neurons behave collectively – that is most strongly linked to the psychedelic state. Mechanistically, this makes some sense. It is likely that this type of increased synchrony has large effects on the integration of information across neural systems that normal perception and cognition rely on. I think that this possible link between neuron-level system dynamics and consciousness is fascinating. It suggests that consciousness relies on a coupled collective state rather than the activity of individual neurons – it is greater than the sum of its parts. That said, this link is still highly speculative at this point. That’s because the phenomenon has not yet been observed in human brains. Also, one should be cautious when extrapolating human experiences to other animals – it is of course impossible to know exactly what aspects of a trip we share with our rodent relatives. But when it comes to cracking the deep mystery of consciousness, every bit of information is valuable. Pär Halje, Associate Research Fellow of Neurophysiology, Lund University This article is republished from The Conversation under a Creative Commons license. Read the original article.

Read More........→August 23, 2023

UFO, Humanity & time travel are the signage of positive index

Concerning about Unidentified flying objects (UFO’S) are only relate to the calculation of their positive ability index. As Positive means development and negative means demolishment, and time is the biggest terms move along with population and its exploration with respect to various field of doing. Productivity is the goal to achieve to move along with time or beyond time. It’s called moving in time frame or doing a rate of time travel. With Respect to earth as model humanity is a very big term of time as it's being with pure value of development with coordination.

As Human has a brain of vision and program with feel and curiosity which are the nucleus of human so we can say so as human we are on earth for managing the earth resources along with its proper utilization and distributions among each as with nature.

So legality is the biggest term of humanity. As it’s manage human in right direction and reduce the rate of resistance among the various field of exploration and their proper integration.

As its being with a rate of positive ability index which is defined the rate of development and human movements on earth as well all across the planetary system.

As it’s a simple formulation of humanity on earth which moves with positive frame of time with the enhancement of its population which is bounded by legal frame work for the positive directions of mass of the people on earth which provides earth explorations and its massive integration provide a rate of productivity which is the sign to do time travel or move beyond time. So acceptance of legal data, terms provides nonstop improvements in the exploration of earth which is a nonstop process runs in infinite terms.

Positive Ability Index of humans mean variable less doings of humans or any species all across the planetary system and as time progresses we use to find the springs of liberty to move far ahead on earth as well in outer space as like UFO’S (advance species with a level of advancement to move on earth or all across the planetary system)

So thinking about UFO’S (Aliens) are as demon is just a myth of imagination if they are not being with positive ability index then their movement in time and advancement is not possible.

So world must need to save itself from any kinds of war, negativity as humanity got current time after the thousands of years of hardship of generations and era of incarnations and once any strong negativity comes then humanity will run in backward of time frame.

So positivism provides explorations with term of infinity and its integration produce a real process of time travel which applicable on universe’s including earth as whole. Positivism is subject to divine and negativity is subject to demon both has time travel on upwards and second downwards. Image Pixabay License, Free for commercial use, No attribution required

Read More........→September 16, 2022

This human footprints found in Tabuk is 85,000-year-old

Tokyo: Human footprints dating back to about 85,000 years have been discovered on the banks of an ancient lake in the Nefud Desert in Tabuk region, Prince Sultan bin Salman, president of the Saudi Commission for Tourism and National Heritage (SCTH), announced in Tokyo on Thursday.

This amazing and rare discovery points to a new understanding of how our species came out of Africa en route to colonizing the world.

Prince Sultan’s announcement came on the sidelines of his visit on Thursday to the exhibition entitled “Trade routes in the Arabian Peninsula – the magnificent antiquities of the Kingdom of Saudi Arabia throughout the ages.”

The exhibition, organized by the SCTH in the Japanese National Museum in Tokyo, is scheduled to end on Sunday.

A joint Saudi international team discovered traces of several adults who were scattered on a muddy land in an old lake — each heading to a different destination — in the northwest of Saudi Arabia, Prince Sultan said, according to a Saudi Press Agency (SPA) report on Friday.

The research team included the Saudi Geological Survey, the SCTH, King Saud University, the Max Planck Foundation for Human History, Oxford University, Cambridge University, Australia National, and the University of New South Wales in Australia.

Prince Sultan said the age of the footprints coincides with the fossil of the finger of an adult person recently found near the central site in the province of Taima.

The finger, whose discovery was announced last month, is considered to belong to an adult of the early migrants in recent times to the Arabian Peninsula via the Nefud Desert, which then was a green pasture replete with rivers, lakes, fresh water and abundant animals – a source of food for humans.

Prince Sultan said the SCTH is working side-by-side with archeologists at the Max Planck Institute that has started work with the commission since several years.

The objective is to study these footprints in detail. The archeological and scientific exploratory works are still going on in international laboratories. Source:  ummid.com

Read More........→May 28, 2018