1. Genes in the News: Making Babies with 3 Genetic Parents
Grace Denny
Chukwuma Mueme
Noah Gilmore
Kaeli Rathmann
Brittany Keroack
Madeline Schroeder
Gianna LaLota

2. Background Info: What is Mitochondrial DNA?
Mitochondria are organelles found in eukaryotic cells, which help with converting energy
In humans, the DNA is circular and double stranded
Mitochondrial DNA is inherited solely from the mother
Very small compared to the DNA in the nucleus. It codes for 37 genes and has around 16,600 base pairs.
This means that there is a 100% chance that a mitochondrial disease will be inherited

3. Background Info: Mitochondrial Diseases
Mitochondrial diseases are caused by mutations
Many of the mutations occur in the genes responsible for the conversion and synthesis of ATP
Occur around 1 in every 5,000 live births
Diseases caused include Kearns – Sayre disease
Possible Solution: Replacing the mother’s mitochondrial DNA
They can be caused by mutations in either the mtDNA or the nDNA.
The diseases are incurable
Symptoms can include blindness, seizures, deafness, muscle weakness, and cardiac defects

4. Oocyte Modification Why is it done? Passed on from mother
For mitochondrial diseases that are caused by mutations in mitochondrial DNA
Passed on from mother
No cure
mtDNA haplotypes “differ in effect on the expression of key health and performance parameters”
Energy production

5. Oocyte Modification: Some Concerns
“cross-talk between genes dispersed across ... nucleus and ... mitochondria.”
“phenotypes with less-than-ideal cross-talk are disfavored by natural selection”
“mitochondrial-nuclear interactions become highly specific over evolutionary time.”
if mitochondrial replacement disrupts these interactions, possible adverse health outcomes

6. Oocyte Modification: The Process
Fertilized nucleus with (mtDNA) with mutation
Nucleus injected into cytoplasm of enucleated donor oocyte with mutation free mitochondria

7. iClicker Question What is the process of oocyte modification?
A. fertilized nucleus with mutated mtDNA enucleated; new nucleus inserted into cytoplasm
B. fertilized nucleus with mutated mtDNA isolated; donor oocyte enucleated; fertilized nucleus inserted into donor oocyte
C. fertilized nucleus with not mutated mtDNA isolated; donor oocyte enucleated; fertilized nucleus inserted into donor oocyte
D. fertilized nucleus with mutated mtDNA isolated; mtDNA removed; not mutated mtDNA inserted into oocyte

8. Pros of Oocyte Modification
It helps to prevent the transmission of some debilitating inherited mitochondrial diseases
Decreases threats of vision loss, seizures and other maladies caused by mitochondrial diseases
Scientists already have promise for oocyte modification
Healthier, future generations

9. Cons of Oocyte Modification
Oocyte modification, at the present state of research, is a step into the dark because researchers have yet to assess the full potency of such genetic engineering
Not sure whether this procedure could actually solve the targeted congenital diseases that may have multiple causes
In some cases the children made through this process have been diagnosed w/ pervasive developmental disorders or abnormalities

10. Cons of Oocyte Modification: Somatic Gene Therapy vs. Germ-Line Therapy
Somatic gene therapy works on a gene mutation of one patient
Germ-line therapy (i.e. oocyte modification) affects not just the patient undergoing the procedure, but every generation after
Embryo created through oocyte modification may likely pass modification to future generation

11. iClicker Question
True or False: Embryo created through oocyte modification are not likely to pass modifications to future generations
A- True
B- False

12. Ethical Ramifications
Marcy Darnovsky, executive director of the Center for Genetics and Society, says that this approach will soon lead to "tampering with other traits such as intelligence or sports ability”
Oocyte modification moves away from the level of treatment into the level of creating humans
In a sense this could be manipulated to become “gene shopping”
 What will we tamper with next?
 Fear of the unknown

13. FDA's Ethical Stance Not tackling ethical questions yet
More focused on potential pros and cons

14. iClicker Question
There are a number of ethical ramifications surrounding oocyte modification. Some critics say that it will eventually lead to us tampering with other traits other than the inheritance of mitochondrial diseases. Overall, do you think that this process is ethically sound? A- Yes B- No C- Not Sure

15. FDA Involvement
Cellular, Tissue, and Gene Therapies Advisory Committee decides level of safety
Determines whether or not it can be used in clinical trials in humans
At this stage the FDA is only taking educational meetings
Ethical issues will not be considered yet
Decision will be made based on scientific merits and preclinical data (assuming it is legal)

16. The UK’s Stance Nuffield Council on Bioethics February 27, 2014
if techniques safe, then process is ethical
mitochondria donation doesn’t equate to multiple parents
February 27, 2014
UK government proposal
allowed only for women who are at high risk of passing on mitochondrial diseases
donors have no parental claim

17. Questions?

18. Works Cited
Taylor, Rebecca "Three-Parent Embryo: Modifying Future generations.” embryo-modifying-future-generations/
Maron, Dina Fine. "Making Babies with 3 Genetic Parents Gets FDA Hearing." Scientific American.N.p., 25 Feb Web. 11 Apr making-babies-with-3- genetic-parents-gets-fda-hearing/
The Ethics of Genetic Engineering by Maureen Junker-Kenny; Lisa Sowle-Cahill. Review by: Peter Whittaker. The Furrow, Vol. 50, No. 5 (May, 1999), pp
Breindl, Anette. "FDA advisory committee grapples with egg cell modification’s scientific side."Bio World. N.p., Web. 11 Apr fda-advisory-committee-grapples- egg-cell-modification%E2%80%99s-scientific-side-0

19. Works Cited
Wilkins, Dr. Jon F. “Maternal Influence.” AccessScience. McGraw-Hill Education, Web. 11 Apr. 2014
Grant, Bob. "FDA Considers Three-Way Babies." The Scientist. N.p., 26 Feb Web. 11 Apr scientist.com/?articles.view/articleNo/39281/title/FDA-Considers-Three- Way-Babies/
“Three parent baby debate” baby-debate-fda-ponders-mitochondrial-manipulation-and-perhaps- germline-modification-too/#.U1GYSManwds
 Reinhardt, Klaus, Damian K. Dowling, and Edward H. Morrow. "Mitochondrial Replacement, Evolution, and the Clinic." Science 341 (2013): n. pag. Print.

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