Let’s celebrate the miracles our ancestors couldn’t even dream of now that science has made them reality

By Dr. Hannah Sivak | May 25, 2025

Andalusians from Jaén,

proud olive growers,

tell me in good conscience who,

who grew the olive trees?

Miguel Hernandez

Some of the miracles my mother dreamed of became reality during her life: the polio vaccine, too late for my young brother but on time for the many millions saved from paralysis and death. Vaccines were made possible by centuries of science and medicine. The polio vaccine prevented millions of deaths and so much misery.

Some people like to imagine the old days, when humans were surrounded by nature and life was easy. Those times never existed, but people can imagine anything they want when they don’t learn from the past. For those who studied history, the past was a time of war, famine, and pestilence, when a single microbe, maybe Yersinia pestis, could kill half of the European population.

I was born in 1948, when the war was over and everything seemed possible. I am happy to say that some of my dreams have come true, at least in the field of science, which I chose as my vocation. Let’s not talk about the other dreams, like the end of all wars and justice for all, because these may be incompatible with the nature of Homo sapiens. Evolution didn’t kill “nice” but didn’t favor it either. We are still at 50/50.

Some dreams of my mother are becoming a reality now. We could have called them crazy in the 1950s. But now? Cure cancer? Done. Not for all of cancers, but for some. And the most magical and impossible of all: to cure inherited metabolic diseases. Of course, many have dreamed of a method that could modify a single, lethal mutation. But the science wasn’t there, not in the 1950s, not in the 2010s. But now? It can be done. “Patient-specific in vivo gene editing to treat a rare genetic disease”.

As Chaim Weizmann said: “Difficult things take a long time, the impossible takes a little longer.” He was referring to the State of Israel, which took almost 2,000 years to be reborn since the Romans won the war against the Jews, dismantled Judea and banned Jews from Jerusalem. Weizmann, a biochemist and the father of industrial fermentation, may have been inspired by what he learned in the laboratory. What you dream of today may be impossible, but eventually, the discoveries and inventions made by scientists like you may convert dreams into reality, if the fault and the solution are implied in the problem to be solved. A “letter” mistake can be fixed with an “editing” solution, if scientific progress allows.

The methodology

What do you need to fix this deadly disease? A misspelled DNA led to a severe deficiency in a newborn’s enzyme carbamoyl-phosphate synthetase 1. Embryos with severe deficiencies in critical enzymes don’t make it to term, but the mother’s body can overcome some of these deficiencies depending on what’s wrong. This baby made it to term, but it was a deadly deficiency that didn’t allow for the complete metabolism of proteins.

First, we need to understand what was wrong: how a single mutation, an incorrect “letter” in the DNA sequence, could result in a faulty protein incapable of doing its job—in this case, an enzyme involved in getting rid of ammonia formed during protein metabolism. Once you find the source of the problem, what can you do to fix it?

“A custom gene-editing treatment”, according to his doctors. The baby received an infusion made just for him and designed to fix his precise mutation. There are so many Nobel prizes (and many more decades of research) involved in that short sentence. The main methoodological advance is “CRISPR”. To accomplish that feat, the treatment is wrapped in fatty lipid molecules to protect it from degradation in the blood on its way to the liver, where the edit will be made. Inside the lipids are instructions that command the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — which was altered to crawl along a person’s DNA until it finds the exact DNA letter that needs to be changed.

What about the future?

Just like the revolutionary COVID-19 vaccine became a model for many more vaccines to come, this genetic editing treatment is a model for treating many deadly illnesses resulting from genetic mistakes, as long as the problem results from one punctual mutation. It could also be used for more common genetic disorders like sickle cell disease, cystic fibrosis, Huntington’s disease, and muscular dystrophy.

Who paid for the scientific advances that made this miracle” possible?

Federal investment in sequencing the human genome made it possible to identify the mutation. Private companies may have provided this baby’s treatment and the many treatments now available for cancer, but the science and treatments they are based on were paid for by us, the taxpayers. The private companies that bring these treatments to the “market” were built on decades of federally funded basic research.

Reference

Musunuru K, Grandinette SA, Wang X, Hudson TR, Briseno K, Berry AM, Hacker JL, Hsu A, Silverstein RA, Hille LT, Ogul AN, Robinson-Garvin NA, Small JC, McCague S, Burke SM, Wright CM, Bick S, Indurthi V, Sharma S, Jepperson M, Vakulskas CA, Collingwood M, Keogh K, Jacobi A, Sturgeon M, Brommel C, Schmaljohn E, Kurgan G, Osborne T, Zhang H, Kinney K, Rettig G, Barbosa CJ, Semple SC, Tam YK, Lutz C, George LA, Kleinstiver BP, Liu DR, Ng K, Kassim SH, Giannikopoulos P, Alameh MG, Urnov FD, Ahrens-Nicklas RC. Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N Engl J Med. 2025 May 15. doi: 10.1056/NEJMoa2504747. Epub ahead of print. PMID: 40373211.

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