Mutation that protects against HIV raises death rate

In this Nov. 28, 2018, file photo, He Jiankui speaks during the Human Genome Editing Conference in Hong Kong. (AP)
Updated 04 June 2019

Mutation that protects against HIV raises death rate

  • The study found that participants with the mutation in both copies had a death rate about 20 percent higher than that of the others
  • About 4,000 participants carried the mutation in both copies, of whom 151 were dead

NEW YORK: People with a DNA mutation that reduces their chance of HIV infection may die sooner, according to a study that suggests tinkering with a gene to try to fix one problem may cause others.
The study authors cited the case of the Chinese researcher who tried to produce this mutation in twin girls before their birth, to reduce their risk for HIV.  His work, which produced the first gene-edited babies, was widely condemned as unethical and risky, and the new paper illustrates one reason for concern.
“You should consider all the effects of mutations you induce,” said Rasmus Nielsen of the University of California, Berkeley, senior author of the paper , released Monday by the journal Nature Medicine.
Nielsen acknowledged that his result cannot be applied directly to the two girls in China. For one thing, his study focused on a sample of people in the United Kingdom who may have different genetic backgrounds than the Chinese girls.
In addition, the people he studied had inherited a specific mutation. The Chinese scientist tried to create the same mutation, but failed. The girls now carry different alterations in the same gene.
The gene is called CCR5. When it is working normally, it lets certain cells of the immune system display a protein on their surfaces. HIV has co-opted that protein to use as a doorway to infect those cells. The mutation prevents that protein from appearing, and so sharply reduces the risk of HIV infection.
Past studies have suggested that carrying the mutation has some drawbacks, including a heightened risk of death from flu.
Nielsen and Xinzhu Wei, also at UC Berkeley, studied data on about 400,000 people who’d signed up between 2006 and 2010 for the UK Biobank, which collected extensive information on them and is following their health. They compared people who carry the mutation in both copies of their CCR5 gene to those who carry it in just one copy or neither, and looked for deaths recorded through February 2016.
About 4,000 participants carried the mutation in both copies, of whom 151 were dead. Analysis focused on deaths between ages 41 and 76.
The study found that participants with the mutation in both copies had a death rate about 20 percent higher than that of the others.  A second analysis showed that at the time participants signed up for the databank, when their average age was about 57, there were fewer people with the mutation in both copies of the gene than one would expect. That’s another sign of a higher death rate.
The researchers were unable to get information on the causes of deaths, so they have no firm explanation for the difference in mortality, Nielsen said. But the heightened risk of death from flu may have played an important role, he said. He also said the size of the difference would probably differ in other groups of people.
Dr. Philip Murphy, an immunologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, said the work provided the first peek at the mutation’s effect on mortality from all causes over a wide swath of the lifespan. “That’s a big deal,” he said.
Nielsen said the study does not apply to a form of gene therapy that differs from what the Chinese researcher did. Some scientists have been inactivating CCR5 in blood cells of people already infected with HIV, to help keep the virus under control. In that situation, having the disabled gene is probably an advantage, Nielsen said.
James Riley, who studies that strategy at the University of Pennsylvania, agreed. Riley said his work affects only a tiny fraction of blood cells, while people in Nielsen’s study with the higher death rate had CCR5 shut off in every cell of the body.
Dr. Anthony Fauci, head of the NIAID, said the new study did not apply broadly to gene editing experiments underway now. Researchers are mainly focused on replacing a defective gene with a working one, or eliminating a harmful one. In contrast, the people in Nielsen’s study were living without a normal, working version of a gene, a condition the Chinese researcher sought to produce.
Fauci said the work is more a lesson that genetic protection against one thing can raise vulnerability to something else.


NASA finds Indian moon lander with help of amateur space enthusiast

Updated 03 December 2019

NASA finds Indian moon lander with help of amateur space enthusiast

  • NASA released an image taken by its Lunar Reconnaissance Orbiter that showed the site of the spacecraft’s impact
  • A version of the picture was marked up to show the associated debris field

WASHINGTON: India’s Vikram lunar lander, which crashed on its final approach to the Moon’s surface in September, has been found thanks in part to the sleuthing efforts of an amateur space enthusiast.
NASA made the announcement on Monday, releasing an image taken by its Lunar Reconnaissance Orbiter (LRO) that showed the site of the spacecraft’s impact (September 7 in India and September 6 in the US).
A version of the picture was marked up to show the associated debris field, with parts scattered over almost two dozen locations spanning several kilometers.
In a statement, NASA said it released a mosaic image of the site on September 26 (but taken on September 17), inviting the public to compare it with images of the same area before the crash to find signs of the lander.
The first person to come up with a positive identification was Shanmuga “Shan” Subramanian, a 33-year-old IT professional from Chennai, who said that NASA’s inability to find the lander on its own had sparked his interest.
“I had side-by-side comparison of those two images on two of my laptops ... on one side there was the old image, and another side there was the new image released by NASA,” he said, adding he was helped by fellow Twitter and Reddit users.
“It was quite hard, but (I) spent some effort,” said the self-professed space nerd, finally announcing his discovery on Twitter on October 3.
NASA then performed additional searches in the area and officially announced the finding almost two months later.
“NASA has to be 100% sure before they can go public, and that’s the reason they waited to confirm it, and even I would have done the same,” said Subramanian.
Blasting off in July, emerging Asian giant India had hoped with its Chandrayaan-2 (“Moon Vehicle 2“) mission to become just the fourth country after the United States, Russia and regional rival China to make a successful Moon landing, and the first on the lunar south pole.
The main spacecraft, which remains in orbit around the Moon, dropped the unmanned lander Vikram for a descent that would take five days, but the probe went silent just 2.1 kilometers above the surface.
Days after the failed landing, the Indian Space Research Organization said it had located the lander, but hadn’t been able to establish communication.