CRISPR is a biomolecular editing tool that allows researchers to “engineer” genes in plants, animals, and humans. Here’s how gene editing has evolved over time
The scientific community received a shock last November, when the Chinese scientist He Jiankui announced the world’s first genetically edited “CRISPR babies”. He is the first known scientist to use CRISPR to edit human embryos resulting in a live birth. Professor He edited the genes of three babies, two twin girls born in late 2018, as well as a third baby due this year. He edited the CCR5 gene in an attempt to give them immunity to HIV infection.
Prof He spurred widespread criticism for his experiment, due to his violation of the unofficial international moratorium on editing human embryos intended for a viable pregnancy. His experiments, which have yet to be verified and examined by the scientific community, have raised many issues concerning gene editing. State and global norms appear to have been violated in the process of the work. The father of the twin baby girls is HIV positive, and the mother wanted to protect them from infection, but the experimental procedure was conducted secretly without research ethics review, and the whole affair has created strong international condemnation and calls for review.
CRISPR: A Breakthrough Gene Editing Tool
Since the 2012 release of the breakthrough study “A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity”, gene editing has been one of the hottest fields of research. This study illustrated how the CRISPR/Cas9 system could cut up a DNA strand at a target location biochemically “programmed” into the enzyme. Over the last seven years, nearly 20,000 papers have been published on CRISPR techniques for manipulating genes. Despite an intense legal battle for the patent rights to CRISPR technology, this field is evolving at lightning speed.
What is gene editing?
CRISPR is short for “clusters of regularly interspaced short palindromic repeats”. The protein Cas9 is an enzyme that acts like molecular scissors, able to snip specific strands of DNA. Genome editing techniques, such as CRISPR allow scientists to modify DNA within a cell. They use ‘engineered nucleases’ to make cuts at specific DNA sequences. The technique can add, remove or alter DNA, which changes the characteristics of a cell or an organism.
Gene editing techniques promise hope for an escape from fate. The previously inevitable code within human bodies can now be changed. However, the technology is still in its infancy. In addition, there is still much not yet understood about how genes are expressed. Unchecked, this technology raises many ethical questions about altering human identity, and scientific ethicists warn that uncontrolled expansion of the technology, like Prof He’s experiment, could lead to disastrous consequences. Though the technology has massive potential to avoid or cure genetic diseases, it raises serious ethical concerns among the global scientific community, particularly in regard to embryonic DNA editing.
CRISPR Babies: An Ethical Checkpoint
Since parents, not children, would consent to the gene editing, Paul Dabrowski, CEO of Synthego, a genome engineering company vocalises ethical concerns. “How do you make sure you can align the person who is consenting and the person who is taking the risk?” Dabrowski asks.
However, parents of children with genetic diseases find hope in gene editing. Marie Ames is one of those parents. A mother of three, her two youngest children have haemophilia. Individuals with haemophilia do not produce enough blood clotting proteins. If her children start bleeding, they won’t stop. “Normal” childhood incidents are painful and dangerous – a new tooth coming in, or a scrape from a fall. Ames says, “If gene editing was around when I was pregnant, I would do it. My kids go through a lot of suffering and pain. I want to save them from that. Of course, safety and side effects are also a concern.”
“Do you think it is fair to bring a child into this world with something like that. A disease that causes suffering?” Ames asks.
The reality is not clear cut. There are many scientists that believe that the potential harm of gene editing to the entire human genome requires extreme caution. On the other end of the spectrum, there are family members and parents that are desperate to improve their loved ones’ quality of life. Prof He’s departure from ethical protocol forces the world to peer ahead into the future of gene editing, but it is impossible to know where the technology is going without examining the history. How did the world arrive to the day of “designer babies”?
Gene Editing Technology Timeline
1856-1863: DNA from the Beginning
Gregor Mendel, called by many the “Father of Genetics”, discovered the fundamental laws of inheritance through his work on pea plants. The Austrian monk uncovered the probability of genes passing from generation to generation by cross-pollinating different pea plant varieties.
1869: The DNA Molecule
Using sources such as pus from bandages and salmon sperm, the Swiss scientist Friedrich Miescher isolated “nuclein,” DNA with associated proteins, from cell nuclei. He was also the first to identify DNA as a distinct molecule.
What does DNA do?
Although the reality is much more complex, DNA can be thought of as the software or “programming” of an organism. Just as software is a set of instructions for a computer to follow, DNA is a set of instructions telling life at its lowest level how to grow, develop, and reproduce. Any errors or “mistakes” in the programming might cause dysfunction or even death of the organism. The variety in DNA also creates much of the normally wide variability in the form of all life: plant, animal and human.
1953: THE DOUBLE HELIX
James Watson and Francis Crick of Cambridge are generally credited with discovering the twisted ladder-like structure of DNA called a double helix. Other Cambridge researchers, such as Rosalind Franklin and Maurice Wilkins, also contributed to the research, but the significance of their contributions might have been recognised until recently.
1961: THE LIFE BUILDER, RNA
The American biochemist Marshall Warren Nirenberg won the Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for discovering how RNA works.
1977: CRACKING THE CODE
British biochemist Frederick Sanger was the first scientist to decode a complete genome. His method of reading genetic code allowed scientists to sequence DNA 1000 times faster than previous techniques.
1983: COPYING DNA
A US biochemist named Kary Mullis invented the polymerase chain reaction (PCR) technique for copying DNA. In a few hours, PCR can make up to 100 billion copies of DNA. PCR is now a central technique in biochemistry and molecular biology.
The term CRISPR was coined by Dutch scientists. CRISPR is shorthand for “clustered regularly interspaced short palindromic repeats.”
2003: THE HUMAN GENOME PROJECT COMPLETED
The US$3-billion, 13-year project developed a much deeper understanding of diseases, mutations, and evolution. A human genome sequence of DNA is now available on the internet to all. The project was only able to map about 92% of the human genome. Key findings include that the human genome has more repeated sections of DNA than previously thought, and scientists are using this data to identify genetic causes for diseases and potential targeted treatments, one form of so-called “personalised medicine”.
Why edit DNA?
In essence, gene editing is similar to editing computer programming. By changing the commands, manipulation changes how the software of the organism functions. Gene editing can be used to:
- Understand how DNA works – Adding, deleting, and modifying DNA will allow scientists to observe changes in organism and cell function
- Treat diseases such as leukemia and AIDS – Genetic conditions and other infections might be cured or treated with genetic modification.
- Modify crops – GMO crops are resistant to pesticides, disease, and drought.
2005: CAS9 PROTEIN DISCOVERED
Alexander Bolton, of the French National Institute for Agricultural Research, discovered the CAS9 protein while studying bacteria.
2012: CRISPR-EDITING TOOL
Jennifer Doudna (University of California at Berkeley) and Emmanuelle Charpentier published a paper about the CRISPR editing tool. Currently, the patent dispute with U.S. bioengineer Feng Zhang is still underway.
- March 2015: Chinese researchers edit first genes of human embryo.
- June 2016: He Jiankui starts project to edit genes of human embryo with live birth.
- March 2017: He recruits couples as test subjects (each with an HIV-positive father).
- Early November 2018: First gene-edited twin girls born. Second pregnancy with third gene-edited baby is reported.
- 25–26 November 2018: Associated Press publishes story of girls’ birth.
- 28 November 2018: He presents study details at gene-editing summit in Hong Kong
- November–December 2018: China’s National Health Commission begins investigation into He’s work.
- January 2019: He was fired from university and censured by health ministry.
- 18 March 2019: A World Health Organization committee plans to meet to establish guidelines for human gene editing.
- August 2019: Third gene-edited baby expected.
Scientists have used gene editing to successfully reduce genetic deafness in mice, created mushrooms that brown less easily, and edited bone marrow cells in mice to treat sickle-cell anaemia. It is unknown whether He’s experiments will result in the successful genetic modification of humans, but it is a major milestone in the development of gene editing technology and a milestone also in the development of a global ethical ‘conscience’ about life-altering technologies.
CRISPR is simple and powerful, but its flaws are relatively unknown. Gene editing can wipe out or rearrange chunks of DNA. The repercussions of such editing are not currently fully understood. Many scientists believe that gene editing on human subjects is premature. Other researchers are working on techniques that might drive the extinction of pests like malaria and Zika-bearing mosquitoes. CRISPR comes with great hope, but also high risk and a mountain of uncertainty. Maybe one day research technologists will eradicate genetic diseases and develop more productive and climate tolerant food supplies, but before designer babies become commonplace, the consequences of CRISPR and other gene editing tools require further investigation.
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