Sabrina Solouki | Graduate student in the field of Immunology and Infectious Disease
In 2005 James Watson, one of the co-founders of Deoxyribonucleic Acid, or DNA, became the first individual to have his entire genome sequenced and made public. Through the Human Genome Project, which utilized revolutionary genetic technology, scientists were able to decrypt Watson’s genetic makeup from a relatively small sample of blood. The collection of all his genes, which make up a person’s DNA, provided the science community with concrete answers to what were simply unknown questions before: one’s predisposition to acquiring a genetic disease, intelligence level, confidence biomarkers, and an array of other physical and personal attributes. Soon thereafter, the technology behind the project responsible for the advancement in genome wide sequencing emerged on the marketplace at a relatively inexpensive cost for consumer use. As might be expected, this commercialized technology rapidly engendered a myriad of concerns regarding privacy, ethics, and policy issues as people began to ponder the implications of having such holistic health diagnoses and/or prognoses made readily available. Although many of these previous concerns about personal genome sequencing have been addressed and laid to rest, in 2016, a new form of genetic technology has taken center stage and is known as CRISPR-Cas9.
This novel genetic biotechnology has transformed the science dialogue, moving light-years beyond questions about one’s hidden genetic code and into questions about modifications of this code. So that now, rather than simply identifying whether a patient has cancer, modifications of the gene associated with the cancer can be targeted to effectively treat the patient. Remarkably, this powerful research tool may not only become the new panacea in the treatment of numerous diseases, but allows researchers to modify a person’s DNA at various levels of development.
In 2013, Jennifer Doudna, a structural biologist at the University of California, Berkeley made a breakthrough in genetic engineering and began the inception of the biotechnology known as CRISPR-Cas9. This system, discovered by exploring bacterial immunity, allowed for the exploitation of bacterial molecules that could be used in precision editing of DNA. Such editing allows for the select targeting of particular genes with very high accuracy rates. Interestingly, Dr. Doudna discovered that some bacteria have the unique capability of employing an enzyme to introduce significant breaks in their genetic code as a mechanism for eliminating deleterious genetic information. Hence through this system, some bacteria are able to fight off harmful viruses or microbes by very precisely cutting the invader’s DNA, rendering the invader innocuous (see review).
The applications of this technology are far-reaching, not only in human systems but animal models. For instance, this biotechnology can be utilized to modify animal organ donors, like pigs, to eliminate foreign pieces of DNA that oftentimes accumulate in their genetic makeup; hence, making such animals a much more safe and effective transplant alternative for humans. Even third-world diseases can be targeted by using this technology on vectors, or insects that transmit disease, producing infertile insects that can no longer spread disease from one host to the next (see primary article). In terms of human applications, CRISPR-Cas9 is galvanizing major science fields like immunotherapy whereby immune cell engineering can be accomplished at high success rates to facilitate the treatment of various medical illnesses. One example includes HIV in which human immune cells are modified to make them impenetrable to the human immunodeficiency virus (see primary article). In support of this, on June 23rd, 2016, the National Institute of Health approved the first human trial of approximately eighteen patients to explore CRISPR-Cas9 gene editing to treat three types of cancer: myeloma, sarcoma, and melanoma (AAAS article on study). But, perhaps the most contentious application this technology allows for is the practice of gene editing on human germline cells. Germline modifications are changes that involve embryos or sperm and possess the exclusive ability to be passed on from one generation to the next. Not surprisingly, this new research tool has sparked an international discussion surrounding its ethical usage as well as questions regarding the appropriate science and technology policy underlying CRISPR-Cas9 to employ genetic alterations at such early developmental stages.
Therefore, like most exceptional advances in science, consideration must be given to the use of this novel technology. Not only do policymakers have a role to play, but scientists must also examine this technology with a prudent mind-set. The pioneer herself, Dr. Doudna, feels so strongly about the responsibility the research community has when employing this system in science that she is now at the epicenter of the conversation surrounding the ethics of CRISPR-Cas9 (International Summitt on Human Gene Editing). Her mission is to assist in the development of policy and awareness to mitigate any misinterpretations by the mass public regarding the technology. Exemplified by her own involvement, Dr. Douda believes that scientists have an important role in educating the public about science and to demystify popular mass media stereotypes to ensure that scientific discoveries are not curtailed by misunderstood spouts of public outcry. Dr. Doudna’s innovative technology has not only revitalized an interest in genetics, but more importantly, it has created a monolithic awareness movement about the responsibility scientists must take in articulating their research to the public.
Primary literature references:
1. Kathrin Schumann, Steven Lin, Eric Boyer, Dimitre R. Simeonov, Meena Subramaniam, Rachel E. Gate, Genevieve E. Haliburton, Chun J. Ye, Jeffrey A. Bluestone, Jennifer A. Doudna, and Alexander Marson. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. PNAS 2015 112 (33) 10437-10442; published ahead of print July 27, 2015, doi:10.1073/pnas.1512503112
2. Pelletier S, Gingras S, Green DR. Mouse genome engineering using CRISPR-Cas9 for study of immune function. Immunity. 2015;42(1):18-27. doi:10.1016/j.immuni.2015.01.004.
3. Zach N. Adelman, Zhijian Tu, Control of Mosquito-Borne Infectious Diseases: Sex and Gene Drive, Trends in Parasitology, Volume 32, Issue 3, March 2016, Pages 219-229, ISSN 1471-4922, http://dx.doi.org/10.1016/j.pt.2015.12.003.