The science here is so cool that I have to make a note of this advance in biomedical technology and treatment. The Food and Drug Administration approved a gene editing treatment for sickle cell anemia last week.
Sickle cell anemia is a genetic disease caused by a single recessive allele. Having two copies of the gene is highly deleterious – that genotype causes sickle cell anemia, in which malformed red blood cells interfere with circulation and cause debilitating pain, organ failure, and cardiovascular disease.
There’s an interesting evolutionary biology story here, too. Because the gene is so harmful, we might expect it to be eliminated from our population over time. But a single copy of the gene confers resistance to malaria. The plasmodium parasite that causes malaria has a hard time affecting red blood cells that carry just one copy of the gene. In places where malaria is endemic, heterozygotes have a fitness advantage. The genes for sickle cell therefore remain relatively common in populations. This is true for much of Africa, including the regions from which people were captured and forced into slavery in the United States. That history of evolutionary biology and slavery has combined to make sickle cell disease much more common for Black Americans than for other Americans.
The CRISPR/Cas9 system uses a combination of bacterial and viral mechanisms to precisely edit the genes of all cells in a living organism’s body. Cas9 is a naturally occurring enzyme in bacteria. It’s a nuclease – an enzyme that cuts up DNA. When some bacteria are infected by a virus, they can produce matching RNA sequences to the viral DNA, which Cas9 can then target, chop up, and deactivate. Cas-9 uses a sequence of short, repeated palindromes to figure out what to target. That’s the CRISPR part of the system (clustered regularly interspaced short palindromic repeats). Cas-9 is also an abbreviation, for “CRISPR-associated protein 9”. I’m sorry for all the jargon and abbreviations, but that’s just how molecular biology is – it’s so complex that we’re constantly inventing new language to describe what we’re studying.
Recently, scientists realized that we could use Cas9 to precisely cut up DNA in people, using a customized RNA sequence to target the spot in the genome that we want to make a cut. We can cut around a mutated gene that isn’t functioning properly and then insert a functional copy of the gene, which will fit into the cut ends of the DNA and result in an intact, functional genome to allow a patient to live a healthy life, free from that genetic disease.
Of course, there are some downsides and caveats to this treatment. First, it’s incredibly expensive. The treatment from Vertex Pharmaceuticals will cost about $2.2 million. An alternative Cas9 sickle cell treatment from Bluebird Bio will cost about $3.1 million. That’s a ton of money. At the same time, living with sickle cell disease is also expensive, costing about $1.7 million over a patient’s shortened lifetime. And that’s a life plagued by constant illness. We can expect more treatment options to become available, and costs should come down over time.
This treatment is difficult, and doing it safely requires a tremendous amount of specialized work. Companies expect that they might be able to treat up to 10 patients per year given their current capabilities. If the treatment proves effective and safe, this capacity will grow, but it will still take a long time to be able to provide treatment to everyone who needs it.
And long-term safety is also a concern. We have no theoretical reason to suppose why there should be long-term health risks. But biology and medicine are complicated; there is still a lot that we don’t know, and there may be unknown risks. I’ll keep paying attention to the new data coming out about these treatments, and I’m excited and optimistic that this is the start of a new era in human health.
ireadthis 