Health  

Safety fears over gene-editing tool, CT scans

*Children exposed to X rays may be at higher risk of developing brain cancer
Safety fears have been raised over a revolutionary gene-editing tool hailed as one of the greatest innovations of medicine in recent decades.

Scientists have warned the genetic damage caused by the Clustered Regularly Inter-Spaced Palindromic Repeats (CRISPR/Cas9) technology – known as CRISPR – have been ‘seriously underestimated before now’.

They have uncovered evidence the gene-editing tool causes unwanted mutations that may prove dangerous – and is ‘much less safe’ than once thought.

Critics fear CRISPR may be used to ‘snip’ damaging genes from children before they are born, such as those that cause Huntington’s disease or blindness.

Others remain concerned it could create ‘designer babies’ by allowing parents to choose their hair colour, height or even traits such as intelligence.

The study adds to the worries, as scientists found CRISPR can introduce hundreds of potentially harmful mutations that standard tests may not spot.

Some trials have made similar findings, with a study last month claiming the tool could cause cancer by making cells less able to repair Deoxyribonucleic Acid (DNA)/genetic material damage.

The work, in the journal Nature Biotechnology, has implications for how CRISPR is used therapeutically and is likely to re-spark interests in finding alternatives.

Also, a study warns children who undergo Computerised Tomography (CT) scans may be at a higher risk of developing brain cancer.

Fears have been raised recent years over the extensive dangers caused by radiation to humans, including cancer.

The new analysis, of nearly 170,000 children who received at least one CT scan, adds to the array of damning trials.

Dutch researchers found the incidence of cancer among the participants was much higher than the average rate.

The new findings, conducted on 168,394 children, were published in the Journal of the National Cancer Institute.

Doctors have turned to CT scans heavily over the past two decades, as they provide a much clearer picture than X-rays.

Patients sit in an X-ray tube, which rotates around their body to take pictures of their internal organs and other parts of the body.

However, the machines also deliver a much higher dose of ionising radiation, which are known to damage bodily tissues.

The researchers found rates of cancer were 1.5 times higher in the children who had underwent at least one CT scan in their life.

But the amount of cancer diagnoses among youngsters who had undergone the most CT scans were four times higher.

Yet there was no link between the scans and leukaemia – even though an array of evidence suggests there is.

Countless trials have debated the contested issue – but some scientists argue there simply is not enough proof.

A landmark study in 2012 found multiple CT scans in childhood can triple the risk of developing brain cancer or leukaemia.

The Newcastle University-led team examined the British National Health Service (NHS) medical records of almost 180,000 young patients to make the finding, published in The Lancet.

What is CRISPR-cas9? CRISPR-Cas9 is a tool for making precise edits in DNA, discovered in bacteria.

The technique involves a DNA cutting enzyme and a small tag which tells the enzyme where to cut.

By editing this tag, scientists are able to target the enzyme to specific regions of DNA and make precise cuts, wherever they like.

It has been used to ‘silence’ genes – effectively switching them off. When cellular machinery repairs the DNA break, it removes a small snip of DNA. In this way, researchers can precisely turn off specific genes in the genome.

The approach has been used previously to edit the HBB gene responsible for a condition called β-thalassaemia.

CRISPR, already used extensively in scientific research, can alter sections of DNA in cells by cutting at specific points and introducing changes at that location.

Wellcome Sanger Institute scientists tested the effects of CRISPR on both mouse and human cells in the laboratory.

An array of trials on the gene-editing tool have shown little unforeseen mutations in the DNA at the target site.

But the first assessment of CRISPR’s unexpected effects revealed it caused extensive mutations – but further away from the target site.

Many of the cells snipped by the technology had large genetic rearrangements, such as DNA deletions and insertions.

Researchers warned these could lead to important genes being switched on or off, which could have major implications for CRISPR’s use in real-life therapies.

Standard genotyping tests for detecting DNA changes missed the genetic damage because they were too far away from the target site to be spotted.

Professor Allan Bradley, study co-author, said: “We found that changes in the DNA have been seriously underestimated before now.

“This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells.”

Why is gene editing controversial? Some have suggested the technology could be used to remove damaging genes from children before they are born, such as those that cause Huntington’s disease or hereditary blindness.

Yet the technology may also be used to insert genes for desired traits, such as blond hair or above-average height.

If science’s understanding of genetics improves, the technology may also one day be used to insert genes that encode certain skills, such as musical ability.

Designer-baby critics also argue only wealthy people could likely afford such technologies.

In the future, health insurers may also reject patients who have not undergone genetic selection out of concerns they have a higher disease risk.

Dr. Louanne Hudgins, who studies prenatal genetic screening and diagnosis at Stanford, adds genetically screening foetuses for diseases is not supported by medical associations and therefore health insurers will unlikely pay for such treatment in the near future.

Critics add people’s upbringings and life experiences also have a substantial impact on traits such as intelligence.

Dr. Richard Scott Jr., a founding partner of Reproductive Medicine Associates of New Jersey, added: “Your child may not turn out to be the three-sport All-American at Stanford.”

Michael Kosicki, first author, revealed it became abundantly clear ‘something unexpected’ was happening during the study.

The researchers then began looking at the effects systematically – to see if the effects of CRISPR held true.

What is a CT scan? A computerised tomography (CT) scan uses X-rays and a computer to create detailed images of the inside of the body. CT scans are also sometimes known as CAT scans, which stands for computerised axial tomography.

During a CT scan, which is painless and takes five to 10 minutes, depending on the part of the body being scanned, patients lie on their backs on a bed.

The scanner consists of an X-ray tube that rotates around the body and the patient is usually moved continuously through this rotating beam.

The X-rays are received by a detector on the opposite side of the body and an image of the scan will be produced by a computer.

The images produced by a CT scan are called tomograms and are more detailed than standard X-rays.

A CT scan can produce images of structures inside the body, including the internal organs, blood vessels, bones and tumours.

The most common malignancies caused by radioactivity among children and young adults are leukemia and brain tumors. Researchers therefore evaluated leukemia and brain tumor risks following exposure to radiation from CT scans in childhood.

The National Cancer Institute, based in the United States (U.S.), lists paediatric CT scans as a ‘public health concern’.

This is because children are more sensitive to radiation than adults, and live longer, meaning there is more times for radiation damage to occur.

In some cases, children may also receive higher doses of radiation than necessary, if the settings of CT scanners are not adjusted.

The new findings, conducted on 168,394 children, were published in the Journal of the National Cancer Institute.

But the researchers, led by Dr. Michael Hauptmann at the Netherlands Cancer Institute, issued caution over the findings.

They said CT scans are sometimes used to identify conditions commonly linked with an increased brain tumour risk.

Hauptmann said: “Epidemiological studies of cancer risks from low doses of medical radiation are challenging.”

“Nevertheless, our careful evaluation of the data and evidence from other studies indicate that CT-related radiation exposure increases brain tumor risk.

“Careful justification of pediatric CT scans and dose optimization, as done in many hospitals, are essential to minimize risks.”

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