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A Crack In Creationr

Gene Editing and the Power To Control Evolution

Jennifer Doudna and Samuel Sternberg

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The simplest mutation is the substitution of one letter. For example, in sickle cell disease, a blood disorder, the 17th letter of a gene called beta-globin, an A has been switched to a T. When translated into amino acids, the change results in the amino acid valine replacing the amino acid glutamate in a critical part of the haemoglobin protein which transports oxygen. The altered molecules cause anaemia and severe bone pain.

This is an example of a recessive gene. If only one copy from one parent, the normal gene produces enough normal haemoglobin. So carriers aren't personally affected, but if they mate with another carrier,their children will only ahve the mutated gene.

Genetic diseases can also result from additions or deletions in DNA. Huntington's Disease is result of 3 letters in the HTT gene repeating too many times (and casues brain cells to produce abnormal proteins which gradually degrades brain). Cystic fibrosis is result of deletion of 3 letters in the CFTR gene.

Big advantage of CRISPR is that it's cheap and easy to use. All scientist needed to do was select the desired 20 letter DNA sequence and then convert that into a matching 20 letter code of RNA. Once inside the cell, Cas9 would slice apart the DNA, and the repair RNA wd pair with its DNA match.

2014 Chinese scientists used CRISPR to alter the six copies of the Mlo gene in bread wheat, which made them resistant to powdery mildew. Other efforts to reduce the level of trans fats in soya bean oil, and to stop conversion od starches into sugars when potatoes are stored.

There are two breeds of double-muscled cattle - the Belgian Blue and the Piedmontese. These cows have 20% more muscle, less fat and a higher percentage of desirable meat cuts. In 1997 it was established that this was due to mutations on a single gene, myostatin, which controls the expression of muscle making proteins. The two breeds have different mutations to this gene. BB cows are missing 11 letters, while the Piedmontese are just missing a single letter, but in both this gene gets knocked out, so muscle growth continues longer than normal.

An unusual child was born early this century with bulging thigh and upper arm muscle. He was amazingly strong Not yet 5, he can hold seven-pound weights with arms extended, something many adults cannot do. He has muscles twice the size of other kids his age and half their body fat. The boy’s mutant DNA segment was found to block production of a protein called myostatin that limits muscle growth. Researchers at Johns Hopkins University in Baltimore created buff “mighty mice” by knocking out the gene that directs cells to produce myostatin. “Now we can say that myostatin acts the same way in humans as in animals.”

Researchers would not disclose the German boy’s identity but said he was born to a somewhat muscular mother, a 24-year-old former professional sprinter. Her brother and three other close male relatives all were unusually strong, with one of them a construction worker able to unload heavy curbstones by hand.

In the mother, one copy of the gene is mutated and the other is normal; the boy has two mutated copies. One almost definitely came from his father, but no information about him has been disclosed. The mutation is very rare in people.

American boy who cd perform iron cross at 5 months old.

Designer pets are on the way. Chinese scientists have bred beagles with the myostatin gene KOed to make them stronger for police work. And given the problems that conventionally bred dogs have bc of inbreeding, CRISPR produced breedscd be a far better option.

The Pyrenean ibex, a wild mt goat, died out in 1999, but genetic material was inserted into the egg of a domestic goat. The birth produced two firsts - the first successful ersurrection of an extinct animal, and, as it unfortunetely died just minutes later, the first time an animal has gone extinct twice.

Gene drives to exploit selfish genes: using CRISPR-Cas9 system in mosquitoes to introduce two genes that cause resistance to the malaria pathogen. The resulting mosquitoes passed on the modified genes to more than 99% of their offspring. Another use of the technique created a recessive gene for female sterility. Since it was recessive, it wd spread rapidly through a population increasing in frequency until enough females had 2 copies, at which point the population wd abruptly crash.

Mosquito-borne diseases cause a million deths a year. CRISPR offers a much more focused way of controlling the insect, and is a lot less toxic than pesticides.

Some people are naturally resistant to HIV. These individuals lack 32 letters in gene for a protein called CCR5, which is one of the parts of a cell's surface that the HIV virus latches onto. But with the deletion, the CCR5 protein can't get to the cell surface, so HIV has nothing to hook onto. Virtually no Africans or Asians have this mutation, but at least 10% of Caucasians have one copy of the gene and 1 or 2% have 2 copies. They are not only totally protected against AIDs but also have less inflammatory diseases. This has already been mimicked with drugs to knock out the CCR5 protein.

Tens of thousands of CRISPR related tools have been shipped all over the world. You can get a DIY kit for $100. This only modifies bacterial or viral genes, but the basic principles are the same, and academic experiments with animal genomes are routinely published. It's not hard to imagine biohackers in a garage fiddling with any genetic system.

Our DNA is constantly changing, at random. Every time our cells duplicate themselves during cell division anywhere between 2 and 10 'mistakes' are made - Every person experiences roughly a million mutations throughout our bodies every second.

If have one copy of gene causing cystic fibrosis, you may have better protection against Tb. One copy of the sickle cell protects against malaria.

We can't wait until we perfectly understand how a treatment works. During the four centuries it took to eradicate smallpox, we had virtually no idea how the human immune system worked.

And if we change a sick person to a healthy person with a gene edit that we know works, we have a far grater certainty than with any new drug.

Nothing organized in process of evo. Its random carelessness can seem like outright cruelty to people unlucky enough to inherit suboptimal genetic mutations.

So ourgenome shouldnot be looked as some perfect precious thing to be preserved at all costs to any individual. It is in fact constantly changing and often in dire need of repair.

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