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Unexpected Risks Found In Editing Genes To Prevent Inherited Disorders

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The genes in mitochondria, which are the powerhouses in human cells, can cause fatal inherited disease. But replacing the bad genes may cause other health problems.

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In September, reproductive endocrinologist John Zhang and his team at the New Hope Fertility Center in New York City captured the world's attention when they announced the birth of a child to a mother carrying a fatal genetic defect.

Using a technique called mitochondrial replacement therapy, the researchers combined DNA from two women and one man to bypass the defect and produce a healthy baby boy — one with, quite literally, three genetic parents.

It was heralded as a stunning technological leap for in vitro fertilization, albeit one that the team was forced to perform in Mexico, because the technique has not been approved in the United States.

The technique is spreading quickly, gaining official approval this month from the Human Fertilization and Embryology Authority in the U.K. The move will allow clinics to apply for permission there to carry out the treatment, with the first patients expected to be seen as early as next year.

But for all the accolades, the method also has scientists concerned that the fatally flawed mitochondria can resurface to threaten a child's health.

Earlier this month, a study published in Nature by Shoukhrat Mitalipov, head of the Center for Embryonic Cell and Gene Therapy at the Oregon Health and Science University in Portland, suggested that in roughly 15 percent of cases, the mitochondrial replacement could fail and allow fatal defects to return, or even increase a child's vulnerability to new ailments.

The findings confirmed the suspicions of many researchers, and the conclusions drawn by Mitalipov and his team were unequivocal: The potential for conflicts between transplanted and original mitochondrial genomes is real, and more sophisticated matching of donor and recipient eggs — pairing mothers whose mitochondria share genetic similarities, for example — is needed to avoid potential tragedies.

"This study shows the potential as well as the risks of gene therapy in the germline," Mitalipov says. This is especially true of mitochondria, because its genomes are so different than the genomes in the nucleus of cells. Slight variations between mitochondrial genomes, he adds, "turn out to matter a great deal."

Mitochondria are the energy powerhouses inside our cells, and they carry their own DNA, separate from our nuclear genome.

The danger lies in the fact that mitochondria are in some ways like aliens inside our cells. Two billion years ago they were free-floating bacteria basking in the primordial soup. Then one such microbe merged with another free-floating bacterium, and over evolutionary time, the two formed a complete cell. The bacteria eventually evolved into mitochondria, migrating most of their genes to the cell nucleus and keeping just a few dozen, largely to help them produce energy.

Today, our nuclear genome contains around 20,000 genes, while a scant 37 genes reside in the mitochondria. And yet the two genomes are intensely symbiotic: 99 percent of the proteins that mitochondria import are actually made in the nucleus.

Mitochondria also still divide and replicate like the bacteria they once were, and that constant replication means that mutations arise 10 to 30 times more often in mitochondrial genes than in the nucleus. If too many mitochondria become dysfunctional, the entire cell suffers and serious health problems can result. Faulty mitochondria are implicated in genetic diseases, as well as many chronic conditions from infertility to cancer, cardiac disease and neurodegenerative diseases. That's because when mitochondria falter, the energy system of the cell itself is compromised.

A three-parent baby could solve the problem by overriding faulty mitochondria, but it also raises the stakes, because the procedure does not completely replace the defective mitochondria with healthy ones.

When the mother's nucleus is transferred, it's like a plant dug up out of ground — a bit of the original soil (in this case, the mother's mitochondria) is still clinging to the roots. That creates a situation that never happens in nature: Two different mitochondrial genomes from two different women are forced to live inside the same cell. In most cases, a tiny percentage (usually less than 2 percent) of the diseased mitochondria remain — but that tiny percentage can really matter.

In his new study, Mitalipov crafted three-parent embryos from the eggs of three mothers carrying mutant mitochondrial DNA and from the eggs of 11 healthy women. The embryos were then tweaked to become embryonic stem cells that could live forever, so they could be multiplied and studied. In three cases, the original maternal mitochondrial DNA returned.

"That original, maternal mitochondrial DNA took over," Mitalipov says, "and it was pretty drastic. There was less than 1 percent of the original maternal mitochondrial DNA present after replacement with donor DNA and before fertilization, and yet it took over the whole cell later."

Mitalipov warns that this reversal might not only occur in the embryonic stem cells; it could also occur in the womb at some point during the development of a baby. Complicating things further, Mitalipov found that some mitochondrial DNA stimulates cells to divide more rapidly, which would mean that a cells containing the maternal mitochondrial DNA could eventually dominate as the embryo developed.

Some mitochondrial genomes replicate much faster than others, says University of California molecular biologist Patrick O'Farrell, who called Mitalipov's research both impressive and in keeping with his own thinking on the matter.

A diseased mitochondrial genome could behave like a super-replicating bully, O'Farrell says, re-emerging and having a large impact on the three-parent baby at any time. It could also affect that child's future offspring. "The diseased genome might stage a sneak comeback to afflict subsequent generations," O'Farrell says. On the other hand, he says, the super-replicators could act as "superheroes," if they carry healthy, fit DNA that is able to out-compete a mutant genome.

The nuclear genes donated by a father could also influence the behavior of the mitochondria in ways we cannot yet predict, O'Farrell says. For example, the father might introduce new genes that favor the replication rate of a defective bully genome. Or the father might introduce genes that help a "wimpy" healthy genome survive and thrive.

Mitalipov's proposed solution to the problem is to match the mitochondria of the mother and the donor, since not all mitochondria are alike. Human mitochondria all over the earth are in a sense a billion or more clones of their original mother, passed down in endless biblical begats from mother to child. Yet, even as clones, they have diverged over time into lineages with different characteristics. These are called haplotypes.

O'Farrell mentions blood types as a comparison. Just as you would not want to transfuse blood type A into someone with blood type B, you might not want to mix different lineages. And while he says he thinks the idea of matching lineages is brilliant, he suggests going a step further. "I say let's ... try to get a match with the dominating genome so that the defective genome will ultimately be completely displaced."

In fact, he adds, the ideal would be to look for one superhero genome, the fastest replicator of all – one that could displace any diseased genome.

To find out which branches are super replicators, O'Farrell hopes to collaborate with other laboratories and test the competitive strength of different haplotypes. Earlier this year, O'Farrell's laboratory published work showing that competition between closely related genomes tends to favor the most beneficial, while matchups between distantly related genomes favor super replicators with negative or even lethal consequences. There are, he says, at least 10 major lineages that would be distinct enough to be highly relevant.

Mitalipov says that most of the time, matching haplotypes should ensure successful mitochondrial transfers. However, he cautions that even then, tiny differences in the region of the mitochondrial genome that controls replication speed could cause an unexpected surprise. Even in mitochondria from the same haplotype, there could be a single change in a gene that could cause a conflict, he says.

In his study, Mitalipov zeroes in on the region that appears responsible for replication speed. In order to find out a mother's haplotype, he says, full sequencing is necessary, and this region from the donor's egg should also be looked at to be sure it matches the mother's. Today, it costs a few hundred dollars to sequence a woman's mitochondrial genome.

But battles between mitochondrial genomes are only one part of the emerging story. Some research suggests that nuclear genes evolve to sync well with a mitochondrial haplotype, and that when the pairing is suddenly switched, health might be compromised.

Research in fruit flies and in tiny sea creatures called cephalopods shows that when the "mitonuclear" partnership diverges too much, infertility and poor health can result. In some cases, however, the divergent pairs are above average and can actually lead to better health.

Swapping as little as 0.2 percent of mitochondrial DNA in laboratory animals "can have profound effects on the function of cells, organs, and even the whole organism, and these effects manifest late in life," according to mitochondrial biologist Patrick Chinnery of the University of Cambridge, writing in November in The New England Journal of Medicine.

Because of all these unknowns, a U.S. panel recommended last February that mitochondrial replacement therapy, if approved, implant only male embryos so that the human-altered mitochondrial germline would not be passed down through the generations.

Most scientists approve of this advice, but biologist Damian Dowling of Monash University in Melbourne, Australia, has reservations about even this solution.

His own research in fruit flies shows that males may actually be more vulnerable than females to impaired health from mitochondrial replacement. Since females pass on mitochondria, natural selection will help daughters sift out any mutations that might be harmful to them, and keep their nuclear and mitochondrial genes well matched. Males aren't so lucky: If mutations don't harm females but do harm males, the males may have to suffer impaired fertility and go to their graves earlier.

This is known as the "mother's curse" — a term coined by geneticist Neil Gemmell of the University of Otago in New Zealand to describe the biological baggage that mothers unwittingly pass down to their male babies.

The bottom line, according to biologist David Rand of Brown University, who studies mitochondrial genomes, is that when you swap mitochondria, the reaction is "highly unpredictable."

And that's why many experts are calling for caution even amid all the excitement following the three-parent Mexico trial — though there is reason to believe they aren't being heard.

A three-person baby has now been born in China, and two more may soon be born in Ukraine, according to Nature News. Zhang, meanwhile, continues to encourage potential patients in Mexico: "We have received interest both locally and abroad," he says, "and we invite people to learn more about the treatment."

Doug Wallace, head of the Center for Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia, is among those calling for a more methodical approach to the technique, though he says he doesn't think there's any way to put the brakes on now. "I think what's happened is we're going to see more and more trials and some families are going to be exceedingly fortunate — and perhaps some will be an unfortunate part of the learning set."

Research on mitochondria has to catch up, Wallace says, and while matching haplotypes is a good idea, it isn't so easy to do in practice. "Finding women to be egg donors is going to be a major limitation," he says — especially when you'd first have to survey a large group to find compatible mitochondrial DNA.

Still, for women desperate to conceive a healthy child this may seem reasonable. Wallace adds that mitochondrial replacement therapy might find favor even outside those seeking to avoid passing on fatal genetic mutations — such as older women simply facing reduced fertility. "There's no proof that's the case," he says, but if it came to pass, that could mean a therapy that might change the DNA of tens of thousands, maybe hundreds of thousands, of babies conceived by this method.

That would have a real impact on the long-term future of society, Wallace adds, and we don't yet fully understand all of the implications.

"I think it's an exciting possibility," he says, "but also a little disconcerting."

Jill Neimark is an award-winning science journalist and an author of adult and children's books. Her most recent book is "The Hugging Tree: A Story About Resilience."

A version of this article originally appeared at Undark, a digital science magazine published by the Knight Science Journalism Fellowship Program at MIT.

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      Restons vivifiant d'un Amour sincère.


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      Cet abondant recours à la vidéosurveillance, devrait-il, nous rappeler un tant soit peu notre Père bienveillant, Jéhovah ? La Bible dit en effet que ses yeux « sont en tout lieu » (Prov. 15:3). Mais cela veut-il dire qu’il examine constamment à la loupe nos faits et gestes ? Nous observe-t-il avec la seule intention de faire respecter ses lois et de nous punir ? (Jér. 16:17 ; Héb. 4:13). Pas du tout ! Il nous observe en premier lieu parce qu’il nous aime et se soucie de notre bonheur (1 Pierre 3:12).
      Jéhovah nous surveille par amour.

      Qu’est-ce qui nous aidera à comprendre que Jéhovah nous surveille parce qu’il nous aime ? Nous examinerons ensemble cinq façons dont cet intérêt se manifeste : 1) Il nous met en garde lorsque nous montrons de mauvaises inclinations, 2) il nous corrige lorsque nous faisons un faux pas, 3) il nous guide grâce aux principes que renferme sa Parole, 4) il nous soutient lorsque nous traversons diverses épreuves et 5) il nous récompense lorsqu’il remarque le bon qui est en nous.

      LE DIEU ATTENTIF NOUS MET EN GARDE

      Premièrement, examinons comment Dieu nous met en garde lorsque nous montrons de mauvaises inclinations (1 Chron. 28:9). Pour bien saisir cet aspect de son observation attentive, voyons comment il a traité Caïn, qui « s’enflamma d’une grande colère » parce qu’il n’avait pas obtenu l’approbation divine (lire Genèse 4:3-7). Nous voyons ici que Jéhovah lui a vivement conseillé de « [se mettre] à bien agir ». Il l’a prévenu que s'il ne changeait de comportement, le péché était « tapis à l’entrée ». Puis il lui a demandé : « Te rendras-tu maître de lui ? » Dieu voulait que Caïn tienne compte de l’avertissement et qu’« [il y ait] élévation », que Caïn retrouve sa faveur. Il conserverait alors une bonne relation avec Dieu.

      Les yeux de Jéhovah voient clair dans notre cœur ; nous ne pouvons pas lui cacher nos inclinations et nos motivations. Notre Père bienveillant veut que nous marchions dans les voies de la justice ; pourtant, il ne nous force pas à changer de route. Lorsque nous allons dans la mauvaise direction, il nous met en garde par sa Parole, la Bible. Comment ? Dans notre lecture biblique quotidienne, nous tombons souvent sur des passages qui nous aident à surmonter de mauvaises tendances ou des inclinations malsaines. De plus, nos publications chrétiennes traitent parfois d’une difficulté contre laquelle nous luttons et nous montrent comment la surmonter. Enfin, aux réunions de la congrégation, chacun de nous reçoit au bon moment les conseils dont nous avons besoin !

      Toutes ces mises en garde, écrite dans la parole, la bible, qu'elles sont vraiment la preuve que Jéhovah surveille chacun de nous individuellement et cela avec amour. Il est vrai que les paroles consignées dans la Bible existent depuis des siècles, que les publications préparées par l’organisation de Jéhovah sont écrites pour des millions de personnes et que les conseils donnés lors des réunions s’adressent à toute la congrégation. Mais dans tous ces cas, Jéhovah dirige l’attention de chacun, individuellement, vers sa Parole, afin que chacun puisse modifier ses inclinations. Ainsi, on peut dire que toutes ces dispositions sont la preuve que Jéhovah te surveille personnellement avec amour.

      Pour tirer profit des avertissements de Dieu, nous devons d’abord comprendre en profondeur sa parole? Quelle aide notre Père aimant nous fournit-il ?


      Lorsque que nous méditons sur la Parole et nous faisons des recherches profondes sur ces principes biblique, nous apprenons à nous corriger intérieurement et ainsi nous nous rendons particulièrement compte que Jéhovah veille sur nous.

      Bien sûr, il n’est pas spécialement agréable de se faire conseiller ou corriger, mais Jéhovah demande à chaque serviteur, de suivre la discipline enseigné dans sa paroles, de part nos yeux, par la méditation, la lecture attentive et en manifester les rappels constant (Héb. 12:11). Réfléchissons à ce que Jéhovah examine en nous. Nous devons être conscient que chaques actions de notre part pourraient nuire à notre relation avec Dieu. Nous devons se soucier de nos sentiments que nous véhiculons envers les autres. Enfin, nous devons être prêt à donner de son temps et de son énergie pour manifester les changements primordiales, à l’aide de la Bible, manifester les actions requises qui mène à plaire à Jéhovah .


      En psaumes 73:24 Le psalmiste a chanté à Jéhovah : « Par ton conseil tu me conduiras » (Ps. 73:24). Quand nous avons besoin d’une direction, nous pouvons « [tenir] compte de » Jéhovah en cherchant dans sa Parole la vrai direction de penser.

      Oui, par sa Parole, Jéhovah nous guide pour nous aider à surmonter les difficultés de la vie si nous demondons à Jehovah de nous guider personnellement.
      Psaume chapitre 37 à lire en entier.

      Pour quel genre de raisons Jéhovah n’intervient-il pas toujour dans nos difficultés personnelles ?

      Jéhovah a peut-être de bonnes raisons de ne pas intervenir dans certaines situations. Imaginons qu’à nos yeux, notre être intérieur fut blessé mais que Jéhovah ait un autre point de vue, que, selon lui, tu as plus de torts, que tu ne le penses. La remarque que tu as trouvée si vexante peut, en fait, être un conseil justifié, auquel tu ferais bien de réfléchir. Dans sa biographie, frère Karl Klein, qui a été membre du Collège central, a raconté qu’un jour, que frère Rutherford l’avait repris avec franchise. Par la suite, frère Rutherford lui a adressé un joyeux « Bonjour, Karl ! » Mais, vexé par la réprimande, frère Klein lui a répondu du bout des lèvres. Comprenant qu’il lui en voulait, frère Rutherford l’a prévenu qu’il risquait de devenir la proie du Diable. Frère Klein écrira : « Quand nous avons de la rancœur contre un de nos frères, surtout si c’est parce qu’il nous a dit quelque chose qu’il était en droit de nous dire dans l’exercice de ses fonctions, alors nous prêtons le flanc aux attaques du Diable. »

      Quand une épreuve semble s’éterniser, nous pourrions nous impatienter. Que faire alors ? Supposons, que nous roulons sur une autoroute et que nous nous trouvons pris dans un embouteillage. Nous ne savons pas combien de temps cette situation va durer. Si nous nous irritons et que nous essayons de prendre un autre chemin, nous risquons de se perdre et, au bout du compte, d’arriver à destination plus tard que si nous avions patiemment suivi le premier itinéraire. Pareillement, si nous restons sur les voies tracées par la Parole de Dieu, en temps voulu, nous arriverons, à la destination prévu.
      Il se peut également que, lorsque nous sommes éprouvés, Jéhovah n’intervienne pas tout de suite parce qu’il veut que nous recevions une précieuse formation (lire 1 Pierre 5:6-10). Dieu n’inflige aucune épreuve (Jacq. 1:13). La plupart des malheurs viennent de « [notre] adversaire, le Diable ». Par contre, Dieu peut se servir d’une situation éprouvante pour nous aider à croître spirituellement. Il voit notre souffrance et, « parce qu’il se soucie » de nous, il veillera à ce qu’elle ne dure qu’« un peu de temps ». Quand nous sommes
      éprouvé, sommes-nous heureux que Jéhovah nous surveille, convaincu qu’il nous ménagera une issue ? (2 Cor. 4:7-9).

      LA JOIE D’ÊTRE APPROUVÉ PAR DIEU

      En fait, Jéhovah examine notre vie pour une raison des plus rassurantes. Par l’intermédiaire de Hanani le voyant, il a dit au roi Asa : « Car, en ce qui concerne Jéhovah, ses yeux rôdent par toute la terre, afin de montrer sa force en faveur de ceux dont le cœur est complet à son égard » (2 Chron. 16:9). Chez Asa, Dieu n’a pas trouvé un cœur complet. Mais si nous, nous continuons à faire ce qui est droit, Jéhovah « montrer[a] sa force » en notre faveur.

      Dieu veut que nous « recherch[ions] ce qui est bon », que nous « aim[ions] ce qui est bon » et que nous « fass[ions] ce qui est bon » afin qu’il puisse nous « témoign[er] de la faveur » (Amos 5:14, 15 ; 1 Pierre 3:11, 12). Il remarque les justes et il les bénit (Ps. 34:15). Songeons, par exemple, aux accoucheuses hébreues, Shiphra et Poua. Alors qu’Israël était en esclavage en Égypte, ces femmes ont craint Dieu plus que Pharaon, qui leur avait ordonné de tuer à la naissance tous les garçons hébreux. Manifestement, leur conscience les a poussées à garder les bébés en vie. Par la suite, Jéhovah « leur fit don de familles » (Ex. 1:15-17, 20, 21). Leurs belles actions n’avaient pas échappé à Jéhovah, dont les yeux « rôdent». Parfois, nous avons peut-être l’impression que personne ne remarque nos belles actions. Mais notre Père céleste y est attentif. Il remarque toute bonne action et il nous récompensera en temps voulu(Mat. 6:4, 6 ; 1 Tim. 5:25 ; Héb 6:10.
      Jéhovah voit tout ce que nous faisons, tôt ou tard, il nous récompensera. En prenant conscience qu’il a l’œil sur nous alors n’ayons pas l’impression d’être sous le regard froid et scrutateur d’une caméra de surveillance. Au contraire, sentons-nous encore plus proche du Dieu bienveillant qui se soucie réellement de nous!


      Revenons à la petite histoire du personnage Amour.
      Avant de vous expliquer le rappels de cette histoire allons lire les paroles de notre Guide JÉSUS Christ.
      Allons en Mathieu 22 :37 à 39
      Alors Jesus lui dit : “ Tu dois aimer Jéhovah ton Dieu de tout ton cœur, et de toute ton âme, et de toute ta pensée. 38 C’est là le plus grand et le premier commandement. 39 Le deuxième, qui lui est semblable, est celui-ci : Tu dois aimer ton prochain comme toi-même
      Mathieu 5:44 à 45a
      Continuez d’aimer vos ennemis et de prier pour ceux qui vous persécutent ; 45 afin de vous montrer fils de votre Père qui est dans les cieux.
      Alors revenons à cet histoire que je transcript au début.
      Nous avions plusieurs personnages, il eut Amour , Richesse, l'orgueil, la tristesse, le bonheur, Le Temps et Le Savoir. Chacun étaient différents en manière de penser, en comportement, pourtant ils parraissent tous ensembles, qu'ils ont réussit leur monde, ils ont ammasé des richesses, leur valeurs en leurs coeur, certains étaient très heureux de leur réussites. Les personnages de cet histoire, aucun personnages ne se montrèrent d'aucune arrogance envers Amour. Richesse, orgueil, tristesse et bonheur ont tous ignoré Amour.
      Amour paraissait être le seul à n'avoir pris aucune précaution au chaos qui venait. Amour avait passé sa vie à comprendre l'Amour de cette vie.
      Il n'avait pas de bateau., il n'avait rien ammassé de cette vie.
      Amour se souvenait que Dieu viendrait le chercher par les nuages matérialisés pour rencontrer le Savoir dans un lieu unique où tout les juste vont.psaime 37'10,11

      Le temps dans cet histoire, qui est le vieillard, est Jésus, Jésus à attendu le signal du Savoir avant de sauver sa brebis, Amour.
      Amour avait transmit à chaque personnages son attention de l'amour, son amour pour son prochain était réel, tous le connaissaient par son Nom "Amour".
      Le temps qui est(Jésus, le viellard) même lui l'a appelé Amour par son Nom.
      Qu'à fait Amour pour rencontrer Le Savoir qui est Jéhovah, comme Jésus il a pardonné les actions de tout ses ennemis, incluant dans sa vie relaté en Galantes 5 :22, 23 par sa maîtrise de soi il a conservé ses 7 qualités, les plus importantes de sa vie et cela jusqu'à presque perde sa vie dans les eaux tumulteuses et il reçu du Savoir, le fruit de L'amour de Jéhovah le Dieu de toutes connaissances, de toutes sagesses et des bénédictions, Amour à reçu  la Récompense  de la promesse qu'il avait attendu toute sa vie.

      Pour finir ce petit discours je vous laisse sur une belle citation de Paul sur le thème de l'Amour.

      L’amour est patient et bon. L’amour n’est pas jaloux, il ne se vante pas, ne se gonfle pas [d’orgueil], 5 n’agit pas de façon inconvenante, ne cherche pas ses propres intérêts, ne s’irrite pas. Il ne tient pas compte du mal subi. 6 Il ne se réjouit pas de l’injustice, mais se réjouit avec la vérité. 7 Il supporte tout, croit tout, espère tout, endure tout. 8 L’amour ne disparaît Jamais, car c'est celui qui aura enduré jusqu'à la fin et les yeux sur fixer sur L'ESPÉRANCE DE LA PROMESSE DE JÉHOVAH LE DIEU DE TOUTES BÉNÉDICTIONS.
      Comme notre petit personnage Amour Notre persévérance nous donnera la chance de recevoir le Prix des juste et des humbles de la terre.
      Cher Serviteurs de Jehovah, annoncons La GLOIRE EN NOTRE DIEU Jéhovah le Dieu de L'Amour, de toutes connaissances et sagesses profondes.
      YHWH ELEON.

      · 1 reply
    • jwdudleyusa  »  Deaf Hear USA

      Good News From God This 32 page booklet will answer many of your Bible questions.
      · 0 replies
    • jwdudleyusa  »  Deaf Hear USA

      Covid-19 - WHAT THE BIBLE SAYS – Matthew 24:1-14
      Satan the evil one controls the earth and mankind.  1 John 5:19.  John 8:44
      Logical explanations for the world’s problems.—Revelation 12:12.
      Reason to believe that our world will change for the better.—1 John 2:17.
       
       CAN WE REALLY BELIEVE WHAT THE BIBLE SAYS?
      Yes, for at least three reasons:
      Satan’s rulership is doomed. Jehovah is determined to bring Satan’s control over mankind to an end. He promises to “bring to nothing . . . the Devil” and undo all the damage that Satan has caused.—Hebrews 2:14,
      God has chosen Jesus Christ to rule the world. Jesus is the complete opposite of this world’s present cruel, selfish ruler. Concerning Jesus’ kingship, God promises: “He will have pity on the lowly and the poor . . . From oppression and from violence he will rescue them.”—Psalm 72:13, 14.
      God cannot lie. The Bible plainly states: “It is impossible for God to lie.” (Hebrews 6:18) When Jehovah promises to do something, it is as good as done! (Isaiah 55:10, 11) “The ruler of this world will be cast out.”—John 12:31.
      TO THINK ABOUT
      What will the world be like after its ruler is removed?
      The Bible answers that question at PSALM 37:10, 11, 29, and REVELATION 21:3, 4.
      Jehovah God truly loves the earth and mankind.  John 3:16
      · 0 replies
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