“As medical research continues and technology enables new breakthroughs, there will be a day when malaria and most all major deadly diseases are eradicated on Earth.”
Peter Diamandis

It seems that I have written about genetic engineering in humans a lot.  Most of the writing has focused on Dr. He Jiankui and his experiments to produce humans genetically resistant to HIV.  For a while, it was not even clear where Dr. Jiankui was, though he was said to be under house arrest. On January 3, 2020, Nature published a news article, “What CRISPR-baby prison sentences mean for research.” This article adds several pieces of information to the CRISPR-baby story.  First, China has confirmed that there was an additional birth.  Dr. Jiankui had previously stated that a second woman was pregnant.  However, the mother was in the earliest stages, so it was not clear whether the pregnancy would carry to term.  We now know that a third child was born.

Second, Chines news announced that Dr. Jiankui and two of his colleges were convicted.  The Chines court said, “in the pursuit of “fame and profit,” He and two colleagues had flouted regulations and research and medical ethics by altering genes in human embryos that were then implanted into two women.” Dr. Jiankui received the most severe sentence of three years in prison while his calibrators received shorter sentences.

While some scientist thinks this is a positive step. “Tang (a science-policy researcher at Fudan University in Shanghai) says the immediate disclosure of the court’s result demonstrates China’s commitment to research ethics. This is a big step forward in promoting responsible research and the ethical use of technology, she says.”  Lu You another scientist worries this could negatively impact other research into CRISPR mediated social health care. “If I were a newcomer, a researcher wishing to start gene-editing research and clinical trials, the case would be enough to alert me to the cost of such violations.”

I suspect that a lot of people will find it surprising that after the controversy over Dr. Jiankui’s use of CRISPR to engineer babies that there is any work going on using CRISPR and humans.  However, not only is their research into using CRISPR to treat human disease, some of this research has reached the stage of clinical trials.  Additionally, this use of CRISPR is a whole different animal from Dr. Jiankui’s work. Now that we have reached the end of Dr. Jiankui’s story, let’s talk about how to do human genetic engineering correctly.

First, when it comes to human genetic engineering, there are two general classifications, heritable and nonheritable. As the name implies heritable means, it can be passed on to children and released into the general population.  In nonheritable genetic engineering, parents cannot pass the genetic changes to their offspring.  In general, the difference between heritable and nonheritable genetic engineering is the cells that scientists genetically engineer.  The nonheritable engineering usually uses cells taken from an adult often adult stem cell.  In both cases, we will be discussing the use of CRISPR to modify adult blood stem cells.

Blood is composed of four components, red blood cells, white blood cells, platelets, and plasma.  The four types of blood cells have a finite lifetime, and the body continually replaces them.  The body uses stem cells to produce new blood cells.  For example, a red blood cell also known as an erythrocyte, develops from the common myeloid progenitor cell (Figure 1 B).  The common myeloid progenitor cell develops from the Hemocytoblast (Figure 1 A), which is a multipotent stem cell.  Hemocytoblasts are a stem cell because when it divides one of the daughter cells regenerates the Hemocytoblast while the other daughter develops into a mature cell type like an erythrocyte.  It is a multipotent stem cell because its progeny can develop into multiple types of cells (Figure 1 D1-10).

In addition to regenerating themselves and producing a differentiating daughter cell, hemocytoblasts can divide to produce two hemocytoblasts.  Since hemocytoblasts can produce two hemocytoblast stem cells, scientists can expand populations of hemocytoblasts.  The ability to expand the stem cells makes them particularly useful for genetic engineering.

Hemocytoblasts can be clonally grown in culture in a lab.  Growing cells clonally means that the population starts from a single cell. Therefore, all the cells are genetically identical.  The specifics of clonal cell culture are not essential to this article, but you can read the basics here. Clonal cell culture gives us the first advantage over embryotic genetic engineering.  When scientists genetically engineer an embryo, the only way to know if the change was successful in all the cells is to test all the cells, which will destroy the embryo.  With clonal cells, you can test as many of the cells as you want and grow more.  Additionally, since the cells are clonal, you know all the cells in the population are genetically the same. 

The other advantage of genetically engineered hemocytoblasts is that they can be transplanted into patients using the techniques for bone marrow transplantation, which brings us to the current generation of CRISPR mediated medical treatments.

The first clinical trial using CRISPR was carried out by oncologist Lu You at Sichuan University in Chengdu, China.  The plan was to use CRISPR to increase the immune system’s response to aggressive lung cancer.  The researchers removed cells from the patents and then disabled the PD-1 gene, which should enhance the immune response.  Dr. You is currently working on a manuscript describing the results of his work. This experiment is not a surprise; genetic engineering of immune cells for the treatment of cancer has a long history.  What CRISPR has added to the technique is a faster, more accurate way to change the cells.

In addition to the cancer work in China, the US has also approved CRISPR mediated medical treatment.  The treatment we know the most about involves Victoria Gray, who suffers from sickle cell anima.  Sickle cell anime is a painful, debilitating disease that causes red blood cells to become misshapen and sticky.  Victoria Gray volunteered to have her blood stem cells engineered so that the red blood cells express fetal hemoglobin which the doctors hope will compensate for the defective adult hemoglobin that causes sickle cell anima.  Victoria received the transfusion of genetically edited cells early this summer (2019) and the results are quite promising.  Doctors will follow Victoria’s progress for months perhaps even decades.  The researchers will also have to repeat the treatment with additional patients.  Using gene editing to treat sickle cell anime is by no means a done deal but for the first-time individuals that suffer from the illness might have a real permeant treatment.

Hopefully, people will be able to see how the work that scientists are doing to engineer adult cells for the treatment of diseases is different from what Dr. Jiankui did.  One of the most important things we need to get across is that there is nothing wrong with CRISPR or gene editing in general.  Gene editing is a powerful research tool with lots of benefits not only for general research but also for medical treatment.  Scientific techniques are not good or bad by themselves; they are only good or bad in how people use them.  After all, I bet Victoria Gray likes CRISPR.

Thanks for Listing to My Musings
The Teaching Cyborg