Medicine is undoubtedly among one of the most lauded fields in the world– there are few who would dispute importance of medical innovation. However, the field is not without controversy, with many new treatments scrutinized for potential ethical or functional issues, as has been the case with the CRISPR/Cas9 gene. Here, Kevin talks to Dr. Andrew Holland at Johns Hopkins School of Medicine to dispel some of the myths surrounding the treatment.
With the rapidly-evolving field of biotechnology, many powerful tools have been developed in order to address the needs of biomedical research, enhancing our field-of-view into the intricacies of the human body from the smallest of molecules to entire organ systems. One such example of a technology that has proven to be critical to the advancement of scientific research is the valuable, yet somewhat controversial CRISPR/Cas9. Already a mainstay in molecular biology studies and cell and tissue laboratories, CRISPR/Cas9 has been infamously claimed as being a method of creating so-called “designer babies.” I sat down with Dr. Andrew Holland of the Johns Hopkins School of Medicine to shine a more precise light into the biotechnology by discussing the work his lab conducts in regards to CRISPR/Cas9 as well as his insights into the technology.
As a member of the Department of Molecular Biology and Genetics. Dr. Holland dedicates much of his work to the study of cell division. Specifically, Holland explained that he and his laboratory are interested in “how cells are able to faithfully partition the genetic information during cell division to ensure that each daughter cell contains all the information that is required for further growth and development.” At every moment, cells are dividing in our bodies, and what remains a mystery, says Holland, is how this process occurs “with such high fidelity” over millions of iterations as well as what the consequences are at the cell and organism levels if errors were to happen during division. Although cell division is a fundamental aspect of cellular biology, the specific processes that regulate how cells are able to carry out mitosis are relatively unknown. However, Holland finds that CRISPR/Cas9 has been instrumental in his work researching how the cell recognizes any irregularities during division and signals for cell cycle arrest.
One of the benefits of using CRISPR/Cas9 is that it has allowed for Holland’s group to “manipulate the genome with relative ease,” thereby enabling them to introduce specific alterations to the genes that responsible for the processes they are interested in and in turn study the function of those alterations. Broadly, this allows for investigation of how these genomic modifications “impact cell division in both in vitro and in vivo models.” In addition, CRISPR has allowed them to conduct genome-wide screening in which they “employ CRISPR/Cas9 to either inactivate or over-express every gene in the genome.” Through screening, they can pinpoint a “certain loss of function or gain of function,” seeing the effect of the changes in the biological pathways of interest.
In response to the dangers of CRISPR/Cas9, specifically the misconception that this technology could be used to create so-called “designer babies,” Holland stated that the “vast majority of people in the world recognize that using CRISPR/Cas9 in the germ line would be completely unacceptable.”
For the application and future of this biotechnology, Holland explained that most people see CRISPR/Cas9 in a therapeutic context, viewing it as a potential method of correcting devastating genetic ailments, such as cystic fibrosis or sickle cell anemia, that deeply affect the quality of life and life span of those whom are afflicted by such diseases. In his opinion, a more accessible, short-term goal of employing this biotechnology in ameliorating the lives of the sick would be targeting the diseases of the blood. “Trying to edit cells within your body to introduce a wild-type copy of a gene by correcting a pre-existing mutation is an incredibly difficult feat when considering the trillions of cells you have in your body” states Holland, “but in the context of blood, it’s possible to take those cells out of your body, manipulate them ex vivo, and introduce stem cells back into the body to allow them to repopulate the hematopoietic system.” Diseases like hemophilia and sickle cell anemia may prove to be correctible in the near future with this application of CRISPR/Cas9, but being able to correct solid tissues is in the distant future. Holland explicated that the issue with applying CRISPR/Cas9 to target solid tissues arises from the fact that there lacks an efficient means of delivering the molecular “scissors” in CRISPR/Cas9 to a large number cells within the body; this is also complicated by how inefficient the process of making precise, minute edits to the genome.
CRISPR/Cas9 has vast, uncharted applications, and with the research scientists like Dr. Holland are conducting, we could soon see how this biotechnology will be used to improve the lives of many debilitated by genetic diseases.