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Doudna Receives the Japan Award for CRISPR

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Doudna Receives the Japan Award for CRISPR

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Jennifer Doudna co-invented the CRISPR with Emmanuel Charpentier. This research project evolved from experiments done to see how bacteria protects themselves from viruses. Bacteria has an intricate immune system that is called CRISPR, and in this immune system has a protein that is called Cas9. Cas9 is able to seek out and cut the viral DNA. The CRISPR system allows that DNA to be extracted from the virus, it gets inserted into a site called CRISPR. CRISPR stands for clustered regularly interspaced short palindromic repeats. This mechanism allows cells to keep a record of infection. Bits of DNA have been inserted into the bacterial chromosome and the cell makes an RNA copy (exact replica of the virus DNA ). The RNA allows for an interaction with DNA because of its matching nucleotide sequence.The RNA binds with the protein Cas9. The complex/pairing then associates itself with the DNA. The protein then cuts up the viral DNA; double stranded break in helix.

CRISPR can be programmed to recognize particular DNA sequences and break DNA in the position of the sequence where there is a mutation. Cells have the ability to detect broken DNA and fix it. Programming the complex to break the DNA at a certain place could allow cells to introduce new genetic information (position of the break could be where the mutation is or the genetic disorder). One type of repair, is when the two helixes of the DNA bind together. The second type of repair is adding a sequence of nucleotide pairings to the broken up DNA. Technological advances and research for genome sequencing has been going on since the 1970s. The technology was either inefficient or hard to use. CRISPR is relatively simple in a way that the protein (Cas9) pairs up with the RNA and creates a very precise incision where programmed.

The technology has been tested on mice to change the colour of their coat. This has been successful and has also been used on monkeys as well. Next steps are controlling theway it is inserted, the off target breaks of cells, and controlling DNA repair afterwards. Within the next 10 years, clinical trials and approved therapies will be brought into the medical field.

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Jennifer Doudna was born in Washington, D.C. on February 19th, 1964. She ended up moving to Hawaii and spent most of her childhood there. Her dad taught American literature at the University of Hawaii and her mom taught history at a local community college. She was surrounded by rainforests, and developed an interest in science when she started exploring them. She first was shown to the world of bio-chemistry when she was in grade 6. Her father gave her The Double Helix, written by James Watson, and she said she could not stop reading it. She then dedicated her high school years to becoming a scientist.

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Breakthrough Prize in Life Sciences (2014)

Princess of Asturias Award for Technical and Scientific Research (2015)

Gairdrner Foundation International Award (2016)

Massry Prize (2015)

Fellow of the Royal Society (2016)

Japan Prize (2017)

BBVA Foundation Frontiers Knowledge Award (2016)

Alan T. Waterman Award (2000)

Eli Lilly Award in Biological Chemistry (2001)

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Doudna ended up at Pomona College in California for her undergrad. She was very interested in the school because of their strong bio-chemistry program. For graduate school, she attended Harvard University. She worked with Jack Szostak, who was a future Nobel laureate. Doudna helped Szostak engineer a self-replicating catalytic RNA. She wanted to continue into the work of visualizing the biochemical activities of RNA, so she went to the University of Colorado for her postdoctoral studies. She worked with biochemist Tom Cech, who was a Nobel Prize winner for discovering the catalytic properties of RNA. She then wanted to identify three-dimensional atomic structures of these molecules, using X-ray crystallography. She continued this work at Yale University in 1994 where she was part of the Department of Molecular Biophysics and Biochemistry, working as an assistant professor. In 2002 she moved to University of California, Berkeley. This is where she continued her studies of RNA molecules. Her research focused on bacteria fighting off viral infections using RNA has flourished. She then spent multiple years writing publishing papers and continuing her research. In 2011, she went to a conference in Puerto Rico where she met her future colleague, Emmanuelle Charpentier. They were both working with CRISPR sequences at the time and decided to use their expertise to advance this technology. She currently holds the Li Ka Shing Chancellor's Chair in Biomedical Sciences at the UC Berkeley.

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A 16-year-old female patient with NF2 tumors

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A 16-year-old female patient with NF2 tumors

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Autosomal Disorder Chart for Neurofibromatosis 

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Autosomal Disorder Chart for Neurofibromatosis 

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Monitoring through yearly check-ups:

Assess skin for new neurofibromas

Blood pressure

Skeletal changes

Eye examination

Surgery:

Tumors and schwannomas

Bone problems like scoliosis

Radiosurgery:

Delivers radiation to tumors without the need of an incision

Cancer treatments for malignant tumors:

Including surgery, chemotherapy, and radiation therapy

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Gradual hearing loss

Poor balance

Headaches

Numbness in limbs

Facial drop

Vision issues w/ cataracts

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Flat, light brown spots on skin

Freckling in armpits or genitalia area

Tiny bumps on iris of eye

Soft bumps on/under skin

Bone deformities

Learning disabilities

Larger than average head size

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Genetically transferred

Autosomal dominant → NO sex link

Chromosome 22 mutation → NF 2 gene

NF 2 gene provides instruction for the production of a protein called Merlin.

Merlin → regulate several key signaling → controlling cell shape, cell growth, and the attachment of cells to one another (cell adhesion)

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Genetically transferred

Autosomal dominant → NO sex link

Chromosome 17 mutation → early on-set NF 1.

NF 1 gene provides instructions for the productions of the Neurofibromin protein

Protein acts as a tumor suppressor →produced in nerve cells (oligodendrocytes and Schwann cells) → surround the nerves.

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There are many ways that CRISPR could negatively and positively affect society. In the situation of the technology advancing to the stage of clinical stages, stakeholders would be affected. Jobs in the medical field that we have now could become more scarce. The reason being that if CRISPR Cas9 starts becoming useful around the world, doctors that dealt with issues regarding genetic disorders could become limited. Although,  we more scientific knowledge can be obtained. Although we think we know so much about science, and that every theory, research, or experiment conducted provides us with information that is set in stone,  it is not true. Regarding this point, we can say that there will always be jobs that will be added to the medical industry as an asset to genome sequencing. A positive effect on society is that countries will not be spending as much money as they would be on long term care of genetic diseases. Since this is a one time operation (from what we know), fixing genetic disorders for adult cells and embryos will be very money and time efficient. Another issue is class division because of who can afford it and not. This technology, once released to the public for medical use, will be moderately expensive. Class divides will become heightened over who will be able to change their phenotype, or even be able to pay for therapeutic treatment.

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Adult cells and embryos of organisms can be genetically engineered therapeutically, but it can also be used selfishly and in an unethical way. Ethical and societal implications that come with genome sequencing could be as simple as regular enhancements of human and animal phenotypes, but it could also be as complicated and futuristic as building war machines. Enhancements of phenotypes include probing the DNA in a way that the person's eye colour is different, or changing how tall they are, or different features of their body that are hereditary. So instead of using CRISPR for therapeutic reasons, firms and companies can exploit the technology to gain profit through "plastic surgery". In extreme cases, if the technology becomes more advanced, ethical implications resulting in human being engineered into having enhances properties could happen. Countries could use the technology to create humans that could possibly be used as warfare equipment/resources. This is a very extreme case, and could definitely be prevented through thought out plans and courses of action that could be taken. In relation to thinking about bioethics and the CRISPR project, Jennifer Doudna has called for a global pause on clinical trials on human embryos.The gene editing lasts for generations to come. This could be an ethical issue because some people might wrongly use the technology to change something in their gene, and it will last forever.  In their lab, Doudna and Charpentier have been testing CRISPR Cas9 on mice and monkeys. Another ethical issue is animal testing. They are using monkeys and mice for depth in research on RNA and Cas9. Doudna wants to make sure that before any clinical trials happen, that the implications are assessed so that there is not any harm that comes to any of the subjects.