If We Can Edit Our Genes, Have We Become Gods?

Dear Reviewer,

Let’s start today with a simple, sobering fact: The Food and Drug Administration, which passes on all drugs administered in the United States, approved the first gene transfer drug trial in 1989. There have been many trials since then, but no gene therapy has been approved. Not one.

People have died in gene therapy trials, most notably Jesse Gelsinger, who, in 1999, died when his immune system reacted to a virus that had been introduced to correct a genetic liver disease. The inflammatory response of his own body to the virus that was being used to get the gene replacement into his liver cells killed him. At that point, the FDA shut down every gene therapy trial underway.

Then in 2003, an apparently successful gene replacement therapy for a boy with no immune system (a so-called “bubble” child, because he had to live in a germ-free environment) went bad when he subsequently contracted leukemia because of the therapy. In 2007, a 36-year-old woman who had received injections of a gene-vectored virus in her knee as part of an arthritis study died when she developed a fungal infection that shut down her organs. The FDA shut down the study.

There have been successes, too. In 2007, one woman and 11 men underwent gene therapy for Parkinson’s disease and none got sick and all had improved motor function for about a year. Meanwhile, Jean Bennett, an ophthalmologist at the University of Pennsylvania, has been doing gene replacement therapy with children who have defective genes in their retinas for nearly 20 years.

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Credit: Baylor College of Medicine Archives
Bubble boy David Vetter was born in 1971 with severe combined immunodeficiency (SCID). He had to remain in a germ free environment all his life. He died at age 12 after an unmatched bone marrow transplant from his sister.

UniQure, a Dutch company whose Glybera gene therapy was the first approved in the world — in Europe in 2012 — has decided not to seek approval in the United States, because the FDA said it wanted the company to run two additional clinical trials.

That says something about how cautious the FDA is about gene therapies.

Glybera restores the lipoprotein lipase gene in patients who have inherited a rare disorder that fails to create the protein. The disease typically causes severe pancreatitis, which in turn often leads to pancreatic cancer.

Obviously, gene editing is fraught with difficulties, but that has not stopped a rush of new biotech companies into the field. The possibilities are simply too spectacular to ignore and new gene editing technologies, like CRISPR, seem to be cropping up all the time. Last November, a biotech startup called Editas Medicine announced it would have a CRISPR based gene trial in humans underway within two years. The CRISPR technology itself is less than three years old.

This Really Is Rocket Science

The potential of gene editing is almost unbelievable. If and when it works, it can permanently cure a disease you were born with after only one injection.

“The potential of gene editing is almost unbelievable.”

Here’s a short list of some common diseases that might be curable or preventable with gene editing: autism, breast cancer, colon cancer, hemophilia, Huntington’s disease, Marfan, Parkinson’s, prostate cancer, retinitis pigmentosa, sickle cell, skin cancer, Tay-Sachs, Wilson, Duchenne muscular dystrophy, Crohn’s, color blindness, cystic fibrosis, Down syndrome, polycystic kidney, Turner syndrome. There are hundreds of other more rare genetic disorders.

But as I’ve said, gene editing is tricky. Nonetheless, the concept is disarmingly simple: Deliver a new correct gene if the inherited gene isn’t producing a necessary protein in cells. Or simply block a gene that is helping produce an antagonist protein.

Delivering the new gene to millions if not billions of cells is problematic, but in recent years, great strides have been made with modified viruses, especially modified adenoviruses, the sort of viruses that cause the common cold. Viruses are incredibly good at getting into cells throughout the body, but the immune system is also good at stopping them. So a successful delivery mechanism — called a viral vector — has to look unthreatening to the immune system but still replicate itself throughout a tissue. To do this, researchers “clip” parts of the virus out, leaving it still able to invade a cell but not viable enough to do harm once inside. The immune system usually passes by a clipped virus.

Then not only must the correct gene be sent to the correct cells, but it must be turned on and it must stay on. Cells have mechanisms to turn off genes that are too active or act weirdly. The new gene also has to become a permanent part of the DNA in a place that won’t cause trouble. The bubble babies who received gene transplants for their gamma-c gene ran into this problem. The gene worked, but it stitched itself into another gene that controls cell replication, so blood cells began dividing like crazy, causing leukemia. One of the five children could not be treated successfully for the leukemia and died.

Some diseases are easier than others, including those of the central nervous system, which is separated from the rest of the body through the blood-brain barrier.

Despite the difficulties, researchers are getting better by the day at perfecting viral vectors and increasingly knowledgeable about how to get genes to go where they want them to go and not go where they shouldn’t.

To your health and wealth,

Stephen Petranek Signature

Stephen Petranek