1. Designer Babies in the Lab.
Giles Palmer, Mitera IVF

2. Background
Science fiction Science today
Wells, Huxley, Gattaca, Bladerunner, •IVF / embryo freezing/ PGD
Splice, Judge Dredd, Halo, Star Wars, •Genome unraveled (1990-2003)
Godsend, The Island, Aliens 4 etc. etc.. •First Artificial organism (Mycoplasma
laboratorium)
•First Synthetic life (Medusoid)
•Dolly (1997)
•Stem cell research
•Nobel prize for cloning research- Gurdon
& Yamanaka

3. What is a designer baby?
• Designer baby- “journalistic
phrase”
• 2004 O.E.D “ a baby
whose genetic make-up
has been artificially
selected by genetic
engineering combined with
in vitro fertilisation to
ensure the presence or
absence of particular
genes or characteristics”

4. Reproductive choice
• Philosophical & ethical debate
• Parents want best for child-good parenting?
• What reproductive freedom do we have?
-Sex selection & family balancing-”Slippery Slope” leading to Neo-Eugenics
-J. Med. Ethics 2002 reported a case where Deaf single women choose
Deaf sperm donor
• Religion/ Beliefs
Greek Orthodox Church-”every human life has a beginning but no end…
…..church ought to maintain reservations”.

5. The case for PGD
• Clinical Application since 1989
• Range of genetic disorders
• PGS-screening for chromosomal
abnormalities.
• Increase pregnancy rate?
• Embryo biopsy safe (Goossens
2008, Liebaers 2010)
• Evolved as genetics has
developed
• Introduction of powerful genomic
amplifying techniques-
a-CGH, SNP arrays and
karyomapping

6. PGD so far…
• 10 yrs. of Data by ESHRE- • Limitations-technical,
27000 cycles mosaicism, timeframe
• Normal embryos-only 42%
• 61% for aneuploidy (Munne 2007)
screening • Oocyte quality, Age of
• 17% single gene disorders Patient,
• 16% chromosomal disorders • Selection often limited in
PGS/PGD cycles
• 4% X-linked disease
• Limited to the genes the
• 2% social sexing
parents already have!

7. IQ
• Not for multiple genes, complex interactions

8. Eye colour
3 genes, still not fully understood:
bey 1 (Chr 15) spectrum/pigment
bey 2 (Chr 15) Brown-Blue
gey 1 (Chr 19) Green-Blue

9. Designing babies
• Healthy Children
• How the parent raises
child is designing
• Human nature seeks and
desires things that are
rare.
• If you want a particular
trait…..

10. Designing babies
• Healthy Children
• How the parent raises
child is designing
• Human nature seeks and
desires things that are
rare.
• If you want a particular
trait…..use time honored
method of choosing a
partner who has the
desired characteristics!

11. The case for saviour siblings /
Bébé Medicament
• Immunogenic typing for bone
marrow transplantation
• If no HLA identical available PGD
can be used to select embryos HLA
identical (or free of disease)
• ESHRE SIG : Interest of sick child
balanced with the interests of future
suggested for neoplastic or congenital donor child.. if parents intend to
diseases effecting the hematopoietic or love child it is non inherently
immune system disrespectful (Hum. Reprod., 2002,
Pennings)

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14. The case for saviour siblings /
Bébé Medicament
•Min time is 12-18 months
•High number of embryos needed
•Age of mother, ovarian reserve
•Success rate of HSC transplantation
•
•HFEA Not to be used for parent!
•UNESCO considers PGD with the
Kant “dignity means that people must only goal HLA typing unethical
always been treated as an end in •No organ transplantation
themselves and never only as a
means”

15. Mitochondrial Transplantation

16. Mitochondrial Transplantation
• Oocyte transfer from fertile
patients- 30 births (Cohen 2001)
• First case of human modification
(mtDNA heteroplasmy)
• “Boost” embryo development

17. Mitochondrial Transplantation
• Mitochondrial disease (1/4000
USA)
• Mitochondrial Research Group
(Turnbull, University of Newcastle)
• Public debate HFEA

18. “Three-parent baby”
• Review health and risks
• Debate about if donor is genetic
parent
Donor contributes 0,1% of DNA
(37 genes)
• Ethically neutral???
• To be continued!!!!

19. Gene Modification
Transgenics
Pharming: Isolate target protein from milk

20. Gene Modification
Gene therapy
use of Vectors to introduce corrected gene
•Target the right cells
•Integrate
Active the gene
•Avoid side effects

21. Gene Modification
Risks
•Marshall(1999) Ornithine
transcarbamylase deficiency:
Adenovirus trial -Death
•Hacien Bey (2003) SCID: Reported
corrected cell function with functional
cytokine receptors
•Transfusion of cells resulted in full
restoration of immune function
•Serious leukemia like disorder 30
months after therapy

22. Gene Modification
Gene therapy
•Murine retroviruses (28%)- first to be used, small load, good targeting
•Adenovirus- larger load, not for clinical studies (safety issues)
•HSV, Pox virus- not widely used
•Non Viral: Naked DNA injection, DNA Lipid complex
•Lentivirus -promising
Cavazzana-Calvo (Nature 2010) 33 months after lentiviral Β-globin gene transfer Adult
with severe Β(E)/B(O) thalassemia “dependent on monthly transfusions since childhood
has become transfusion independent for last 21 months”
•Artificial chromosomes-YAC, BAC, MAC and HAC

23. Gene Modification
Artificial chromosomes

24. Gene Modification
Gene therapy
•Murine retroviruses (28%)- first to be used, small load, good targeting
•Adenovirus- larger load, not for clinical studies (safety issues)
•HSV, Pox virus- not widely used
•Non Viral: Naked DNA injection, DNA Lipid complex
•Lentivirus -promising
Cavazzana-Calvo (Nature 2010) 33 months after lentiviral Β-globin gene transfer Adult
with severe Β(E)/B(O) thalassemia “dependent on monthly transfusions since childhood
has become transfusion independent for last 21 months”
•Artificial chromosomes-YAC, BAC, MAC and HAC
•Spermatozoa ( ICSI or injection into testis)- Winston, Wilmut

25. Germ line Modifications
• IBC: Germ line interventions could be contrary to human
dignity, rejects idea of testing/enhancing any human
characteristic other than to alleviate suffering
• Council of Europe 1997 a.13: ”an intervention seeking
to modify the human genome may only be undertaken
for preventative, diagnostic or therapeutic purposes and
only if its aim is not to introduce any modification in the
genome of any descendants”

26. The case for cloning
Pros Cons
•Clone of deceased child •Loss of human dignity
•Duplicate individual of Great •Unjustified power over clone
genius, beauty, physical ability •Welfare of the clone
•Health issues
•No reason to!
•Inefficient
•Identical?

27. The case for cloning

28. Health issues
•
• Pregnancy •
Mortality
Late puberty
• Spontaneous abortions • Decreased Lifespan
• Abnormalities-placental, low cotyledon • Rapid aging
count, thickening fetal membrane,
Hydrallantois, Edema of placental
• Cloning skips gametogenesis
membranes, hypertrophy of
cotyledons, Edema of umbilicus • Reprogramming/imprinting/telomeres
• Retarded development, abnormal
growth curve, abnormal expression of
mRNA
• Post natal-
• large birth size, in adequate organ
development, lung dysmaturity,
respiratory distress, metabolic acidosis
Shoemaker 2006, Bertolini 2004, Lee 2004, Kato 2002, Xu
2000, Okonuki 2002
• Inefficient THCR (1-4%)

29. Use of Stem cells

30. Use of Stem cells

31. Stem cells
• Therapeutic cloning use the cloning • Reproductive cloning procedure to produce
procedure to produce a clonal embryo clonal embryo transferred to the uterus with
to generate stem cells the intent to recreate a living organism

33. Generation of Chimeric Rhesus Monkeys
• Totipotent cells in early embryos are progenitors of
Cell, January 2012
all stem cells and are capable of developing into a
whole organism, including extra embryonic tissues
such as placenta. Pluripotent cells in the inner cell
mass (ICM) are the descendants of totipotent cells
and can differentiate into any cell type of a body
except extra embryonic tissues.
• The ability to contribute to chimeric animals upon
reintroduction into host embryos is the key feature
of murine totipotent and pluripotent cells. Here, we
demonstrate that rhesus monkey embryonic stem
cells (ESCs) and isolated ICMs fail to incorporate
into host embryos and develop into chimeras.
However, chimeric offspring were produced
following aggregation of totipotent cells of the four-
cell embryos. These results provide insights into the
species-specific nature of primate embryos and
suggest that a chimera assay using pluripotent cells
may not be feasible.

34. The Clone Laws
• Inspired by WHO, WMA, Helsinki Declaration on Biomedical Research,
CIOMS
• Convention of Human Rights and Biomedicine (1996)- Ban on Genetic
research performed on humans, creation of h-Embryos for research
• Council of Europe (1997)
a.13: ”an intervention seeking to modify the human genome may only be
undertaken for preventative, diagnostic or therapeutic purposes and only if
its aim is not to introduce any modification in the genome of any
descendants”
Forbids “any intervention seeking to create a human being genetically
….identical to another human being, whether living or dead”
• UNESCO-Universal declaration on Human Genome and Human Rights
(1997)- Germ line modification - contrary to human dignity
• UN General Assembly (2001) Committee against Reproductive cloning
(UN cloning treaty 2003)
• ESHRE-Extended moratorium of human cloning

36. Hybrids and Chimeras
*

37. Mitochondrial Transplantation
II
• Review HFEA
• Ooplasmic Transfer (OT)
• Abnormalities ( Jacob 2006, Brown
2006)
• Needs 50% to be effective so…
• Nuclear Transfer (NT) into
enucleated oocyte
• 1.Nucleus of Unfertilized oocyte (De
Wert 2000)
• 2.Pronuclear transfer (Brown
2006,Turnbull 2010)
• 3.Blastomere nuclear transfer (De
Wert 2000)
• Safety issues- mtDNA influence?
• Ethical issues-is it Germline
intervention???
Prohibed by Council of Europe 1997

38. Mitochondrial Transplantation
II
enucleated oocytes
ET • NT type 1
• NT type 2
ET
ET • NT type 3
If also ET isn’t this reproductive cloning ????

39. Mitochondrial Transplantation
II
• In grating a license for
research to Newcastle
University shown mtDNA ≠
nDNA NOT GERMLINE
• Strong consensus that
mtDNA does not alter or
influence character ?
• ? Cognitive capacity in mice
(Thorburn 2001),
• ? Facilitate Athleticism
• Debate continues

40. Moral status of the embryo
Hippocratic prescription
“ἀ σκέειν, περὶ τὰ νουσήματα, δύο, ὠ φελέειν, ἢ μὴ βλάπτειν”
Research, treatment and diagnosis effecting the genome should be undertaken
only after rigorous prior assessment of potential risks and benefits
Care to protect the vulnerable infertile couple to allow optimum chance of
becoming parents with respect to all stages of the embryo
Genetic screening for Medical indication  …..rest needs more debate