One of the privileges of writing a blog is that you can look back at older posts and see how they hold up over time. One of the first posts I made was back in March 2017 (Greatest Thing Since Sliced Bread? Sliced DNA!) discussing a technology called CRISPR. Since that time, the founders of the technology have won a Nobel prize, and just within the past week came word that a test returned its first results with stellar responses. An intractable and fatal genetic disease appears to be successfully treated via internal application of CRISPR-modified material. It is very early in the process, and the market for this particular disease is very small, but the response in the stock market was explosive. Fortunately for me, I had put money on two of the stocks in this field, and I am experiencing the volatility of the biotech field in my investments.
Here is the text of the original post. I haven’t changed a word since the potential benefits and potential adverse effects still hold true. You may have heard that a rogue scientist in China crossed an ethical line and treated twin fetuses with CRISPR. In that case, it was to remove the potential to be infected with HIV as opposed to treating a genetic defect. That is still not allowed, and the scientist was punished.
Over the past decade, a new technology has emerged, begun commercialization, and provides amazing potential to revolutionize biological science. My guess is that you’ve never heard of this incredible advance in biology. So let me introduce you to: CRISPR. As is often the case, CRISPR is an acronym. It stands for: Clustered regularly interspaced short palindromic repeats. Having given its full name once, let me just say that it refers to how it deals with DNA inside of a cell.
CRISPR (pronounced Crisper) is a modification of a naturally occurring process in bacteria. Just as we are attacked by pathogenic bacteria, bacteria themselves are attacked by viruses called bacteriophages. These phages are able to hijack a bacterial cell’s DNA and inject portions of their own DNA that then enables replication of the phage, allowing the copied phages to burst through the cell wall and kill the bacteria. Naturally, it is to the bacteria’s advantage to detect and remove the rogue DNA. And evolution has developed a tool, in the form of a set of genes that enables detection of an alien DNA sequence, and essentially cuts it out and puts in its own jumper that bypasses the infected area. So nature has developed its own DNA repair process that enables a bacterial cell to detect infection, remove the infection, and repair the DNA to allow it to continue to function. Only the non-functioning repeated DNA segments is left in the DNA to show that the repair has taken place.
Researchers have discovered this process, and developed an improved process based upon it. Companies have formed around the technology, and other companies have licensed the technology and are actively working on applications. This process is just beginning, and it is one of the most exciting new developments in biology in decades.
CRISPR technology is far different than the genetic modifications that have been used in agriculture that stir deep revulsion in many. The process that Monsanto and DuPont and other agribusinesses use to produce seed that is resistant to herbicides requires the insertion of genes that are from another organism. This crossing of species creates what is called “Frankenfood”, and many nations have forbidden the use of foods created with this technology. CRISPR technology does not involve alien genes. Instead, it allows for the CRISPR process to inactivate genes by excising and bypassing the undesired section. This has huge potential application in human health, because many genetic-based diseases are caused through a fault in one of the genes. This faulty gene may create a faulty protein that causes the genetic disease. If you can simply snip off the bad part, and replace the gene with either a nonsense segment of DNA that does nothing, or a fully-functioning gene that works as nature intended, then you now have the potential to reverse a genetic disease.
CRISPR is being used to develop food seeds like the ones from Monsanto and DuPont. But in this case, species lines are not being crossed. Instead, normal plant breeding practices can be used to develop desirable traits, and the genetic technology can be used to greatly increase its effectiveness in the seeds. This eliminates the fear factor that previous genetically modified organisms generated.
The mechanics of how to introduce the desired genetic fix into an organism is one of the greatest uncertainties of how this technology will be used. Obviously, the smaller the organism, the easier it is to fix. That’s why some of the first applications of the technology are for things like industrial yeasts that ferment vegetable matter to convert it to ethanol for fuel. One of the limiting factors in bioethanol production, is that the alcohol becomes lethal to the yeast in too high a concentration. By working with strains of yeast that show greater resistance to high concentrations of alcohol, and by inserting the genes from these strains into other strains of yeast, the potential is there for greatly increased efficiency in bioethanol production. The technology is well developed for insertion of genes into seeds as well. So the earliest commercial applications are for agribusiness and biofuel production.
It is a far different task to introduce the fix to a genetic problem to a complex organism like a person. One area of early research involves the eye disease retinitis pigmentosa. This disease is genetically inherited, and eventually causes the retina to degrade, resulting in blindness for one and a half million people worldwide. The proposed treatment involves taking cells from the person with the genetic trait, converting them into stem cells, fixing the genetic defect with CRISPR technology, and transplanting the cells back into the retina of the person with the disease. There is a possibility that a human trial using this technology may happen in 2017. The gene repair process can work where the affected area is small in scope like the retina. How this can work in a disease that is expressed throughout the body has yet to be determined.
One obvious way the technology could be used is when the human with the genetic defect is still in the womb. Genetic tests that can detect inherited diseases are available during pregnancy. Eventually the potential will exist to provide a fix for an inherited genetic disease before birth, eliminating the disease before it happens.
That last bit is one of the ethical areas that must be fully discussed and agreed to by all before the technology is adopted for use in the womb. Any change that is made in the genome at this stage is able to be transmitted across generations. So far, there has been an agreement that genetic modifications should not be allowed if the modification can be inherited by subsequent offspring. The potential to eventually eliminate diseases like cystic fibrosis, Huntington’s chorea, Parkinson’s, and Alzheimers through this technology may be irresistible, and may eventually force the moral issues emerging from this technology to be addressed.
This field is emerging and growth in the field is exponential. I am a reader of Science magazine, and only became aware of this technology since CRISPR was declared the science development of the year in 2015. Since that time, multiple commercial companies have been created, some of which had their IPO last year. It is my prediction that within the next two years, this technology will become widely known and discussed, and remember, you heard it here first.