Leigh Babineaux
Project 107
UNIV 100
21 November, 2017
Genetic Editing
ABSTRACT
This paper explores the medical ethics of the manipulation of the human genome in
fetuses with CRISPR-Cas 9, more commonly know to the public as designer babies. Now there
are several factors that must be looked at to determine the efficacy of genetic editing. The major
factors this essay explores are: how is it done, what are the side effects, what are its uses, and
what are its alternatives. Through scientific inquiries, and not science fiction based fear, this
paper explores the ethical standpoints on the alteration of the human genome.
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What if there was a way to change the one thing that truly made us physically human? To manipulate the very genes that separate the human species from any other living organism? To alter DNA and eradicate certain genetic disease forever? Imagine a world where not only could a parent ensure that their child was free from the burden of any genetic abnormalities but have the ability to theoretically determine any and every traits of their offspring. Within this decade this idea, once only believed to be science fiction, is being developed and utilized through the gene selection process formally known as CRISPR-Cas 9 1. For now this groundbreaking tool is being used in laboratory settings but as capitalism pushes its ever present head into the scientific community, one must be prepared to argue the ethics of genetic manipulation for non-medical purposes. Commercialization of such a powerful and historic innovation raises several questions. Should something that could very well alter the fate of the human species as we know it, be determined by the same species that brought the world such horrific inventions like as
Sandwich in a Can?
For many science fiction enthusiasts the term “designer babies” would evoke terrifying and hair raising images from such movies as Gattaca 2 or Splice 3. While the very idea of mere humans having the ability to manipulate genetic code seems completely outlandish, technological innovations dating back to the late 1990s have been leading up to this very moment. For the first time in human history, the question is no longer could we manipulate the human genome, but should we and to what extent. Is this scientific development the answers to the ill or is it an illusion made of wax and feathers much like the wings of Icarus 4 from Greek mythology?
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The true ethical dilemma comes into play when assessing whether or not it would be
helpful or harmful to manipulate a child’s genetic makeup. According to Dr Daryl F. Sas and
Hannah Martin Lawrenz in their paper "CRISPR-Cas9: The Latest Fashion in Designer
Babies.", “[as] long as the benefits of the technology appear to outweigh the risks—a strictly
consequentialist view—it is ethical to use” (86). But what are the technological benefits and risks
and when does one decide when one risk outweighs the other? In the case of genetic
manipulation, there seems to be a general consensus that any child is better off without any
biological deficits but what about in the case of any other trait? Is a child better off with blue
eyes instead of brown? Or blond hair instead of red?
Although the desire to continue one’s genetic lineage is personal, the refashioning any genetic aspect of a living creature would qualify the creature as a Genetically Modified organism
5, or GMO; therefore alteration of the human genome should be regulated by the Inter-
Ministerial Commission For Safety of Genetically Modified Organisms (CIBIOGEM)6. In 2005, the commission outlined their function with the Law on Biosafety of Genetically Modified
Organisms that was “created in order to manage potential risks associated with GMOs and promote the ethical development of this area of biotechnology” (Chan 431). However, the Inter-
Ministerial Commission For Safety of Genetically Modified Organisms (CIBIOGEM) denies
responsibility for determining the efficacy of designer babies. They claim that the law is
“essentially symbolic” in the case of genetic modifications within the human genome because of
the “[stipulation] that ‘human beings’ are not considered ‘organisms’ for the purposes of the
law” (Chan 431). This left various group to come to their own conclusions and further impede a
unified opinion on its efficacy.
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Until recently there has been no true overseer regulating this procedure because it seemed
to fall between the cracks of each regulator agency’s responsibilities. While this flux of power
was going on, the only unified response from the biomedical community as a whole was that
“gene editing to create children [is] impermissible at the present time” (Chan 428 ). Finally after
years of an ethical standstill, the U.S. Food and Drug Administration (FDA) has taken over this
responsibility (Kozubek). They are classifying CRISPR-Cas 9 as a drug because of its ability to chemically modify a cell (Kozubek).
While exploring the efficacy of gene selection, first one must look at the processes in which DNA is altered. In a breakthrough drug Exondys 51, improperly placed stop codons are altered by the replacement of a single base pair (Babineaux 1). This drug is given intravenous on a bi weekly basis to sufferers of Duchenne Muscular Dystrophy 7 (Babineaux 1). This treatment
is the first of its kind to go into an adolescent's DNA and inhibit the reading of the stop codon in
the next DNA replication (Babineaux 1). With Exondys there is little concern about the alteration
of the germline 8 and its affects future offspring, because those afflicted with Duchenne
Muscular Dystrophy that live to see their reproductive years are in no physical condition to
procreate (Babineaux 3).Unlike Exondys that is used long after the primary stages of DNA
formation and cell development, any genetic modifications in vitro could eliminate the chance of
a trait being passed down to future offspring. For this reason, many scientist fear that if these two
types of DNA alterations are not distinctly separated that “gene editing research would be ‘tarred
with the same brush’, impeding valuable science” (Chan 428 ).
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One concern on genetic alteration is the chance of any genetic abnormalities altered in one generation would still be passed down to the next; however, new scientific developments proves that this would not be the case. Ironically it is the exact opposite occurrence; any change to the parent DNA will affect their offspring. Not only is this a side effect of genetic modification, but one of the results for which it strives. As Dr Stephen L Baird, Director of
Pathology and Laboratory Medicine at UC San Diego states, “Germline engineering seeks to affect the genes that are carried in the ova and sperm, thus eliminating the disease or disorder from all future generations, making it no longer inheritable”(14). Many advocacy groups argue that the use of germline manipulation be used only for “clinical reproductive use and calling for measures to ‘[s]trongly discourage, even in those countries with lax jurisdictions where it might be permitted, any attempts at germline genome modification for clinical application in humans’”
(Chan 428).
Of course, there are limitations on how traits are selected at this point in time; natural conception and genetic manipulation can not currently be used hand in hand. Any gene manipulation must take place in a laboratory. According to Dr Baird:
“Germline modification would begin by using [In Vitro Fertilization] to create a single-
cell embryo or zygote. This embryo would develop for about five days to the blastocyst
stage (very early embryo consisting of approximately 150 ceils. It contains the inner cell
mass, from which embryonic stem cells are derived, and an outer layer of cells called the
trophoblast that forms the placenta. (It is approximately 1/10 the size of the head of a
pin.) At this point embryonic stem cells would be removed. (Figure 2) These stem cells
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would be altered by adding genes using viral vectors. Colonies of altered stem cells
would be grown and tested for successful incorporation of the new genes. Cloning
techniques would be used to transfer a successfully modified stem cell nucleus into an
enucleated egg cell. This "constructed embryo" would then be implanted into a woman's
uterus and brought to term. The child born would be a genetically modified human
{Inheritable, 2003)” (14).
Since this procedure is fairly new, there are several problems associated with it. The two major risks would be the chance that if the procedure takes place after a certain time stamp the fetus could develop mosaicism 9. In even worse circumstances, the wrong gene has been accidentally cut on or misplaced(Sas 86). This mishap begins when the CRISPR molecule sends an enzyme, commonly Cas 9, to “chop the code like tiny molecule scissors” as Jim Kozubek from the New York Times states in his article “How Gene Editing Could Ruin Human
Evolution.”, Cas 9 is not known for its precision, so during the “jerry-rigged repair” in which the enzyme “[incorporates] small bits of available DNA or a repair template of other genetic material that scientists might add” misplacements are known to occur (Kozubek).
According to Tuhus-Dubrow, it is likely that the court cases Connecticut v. Griswald
10(1965) and Roe v. Wade 11 (1973) will have inadvertently set the legal groundwork in the future case of selecting traits. The case of Griswald v Connecticut ensures a couple “right to privacy in marital relations” and, therefore, if a child were to be conceived and their DNA edited for any reason, it could be argued that the choice to alter their child’s DNA is a form of marital relation
(Griswald v Connecticut). In the case of Roe vs Wade, the key phrase for the argument is the
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phrase “total autonomy”. Total autonomy would completely warrant the manipulation of a fetus’
DNA as much as the termination of a fetus would.
Even without the use of genetic editing, artificial trait selection is in use for couple who rely on in vitro fertilization for conception (Sas 84). In these cases zygotes that test positive for disorders like Down’s Syndrome, Huntington’s Disease, Cystic Fibrosis, and Sickle Cell during preimplantation genetic diagnosis (PGD) are simply discarded in favor of zygotes that tested negatively. The ethics of this is not condemnable in the scientific community because in non laboratory settings “90% of pregnant women who receive a prenatal diagnosis of Down
Syndrome through amniocentesis” aborted the pregnancies (Sas 84). Prior to 2002, the only choice expecting mothers had when the Maternal serum alpha-fetoprotein (MSAFP) test11 came back positive was to either terminate the pregnancy or wait it out and deal with this varying and in many cases debilitating disease their child may have (Myelomeningocele). This can be a tremendous financial burden. According to the Center of Disease Control, the cost of getting the proper care and necessities for a child with spina bifida can add up to from anywhere between
$21,900 to $1,350,700 dollars over a lifetime. Genetic editing would save parents collectively millions of dollars each year as well as alleviate parents of the emotional toll these defects bring.
In addition to the financial obligation these defects are often debilitating for those afflicted and require a lifetime commitment from the family. It is for that reason it can be said with certainty that the eradication of genetic abnormalities that threaten overall quality of life of everyone involved is far from the ethical dilemma at hand.
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Alone, preimplantation genetic diagnosis does not “pose no new eugenics dangers”(Baird
14). The danger presents when parents who, as Professor Alan Handyside of the University of
Leeds phrases it in his lecture “Twenty years of designer babies” , “want to know (or control) how their child will turn out and whether they will be healthy.” While the sentiment of a parent wanting their child to be completely healthy is understandable and even endearing, with CRISPR technology as it is there would be no way to make a child “completely” healthy. With every edit made to the DNA chain several important genes get displaced; similar to Newton’s third law of motion 13 there has to be some sort of give in take. Having said that these factors alone do not
make gene selection unethical.
The practice of trait testing and discarding itself does not become unethical until the
determining trait is gender (Baird 13). The allowance of parents choice of gender selection in
commercial cases could potentially destroy the balance of gender. Such imbalance would wreak
havoc on the human population. However, there are certain instances in which gender selection
is not completely unethical; in cases where disease are gender specific or X- linked it can be
argued that it is not a gender bias but merely a concern about healthy offspring.
There are two abilities of this procedure that are also highly controversial. The first
innovation involves the “mitochondrial replacement therapy 14” (MRT) which could allow for
“three-parent embryos”” (Sas 84). The other innovation will allow for 100% accuracy in the case
of savior siblings 15. The creation of “embryos for tissue matching” are no different from the use
of savior siblings (Baird 13). However, unlike with savior sibling where matching genes is not a
complete guarantee these zygotes are “created to be donors” by being “tested for a tissue match
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with a sibling that has already developed, or is in danger of developing, a genetic disease or disorder”(Baird 13). Of course this issue reeks of an ethical dilemma all on its own.
Modern, more science based Genetic engineering began with in vitro fertilization but the groundwork began with Mendel and his pea plants 16 , who gave us the science behind what had been done for millennia (13). As Baird points out “[g]enetic engineering in its broadest sense has been around for thousands of years”(13). Humans would breed animals and plants to produce various species. It is for these reasons bananas are long and seedless, dog breeds exist at all and cows produce as much milk as they do. The simple truth is that selective breeding, also commonly known as artificial selection, is not only a common occurrence in human history but a pillar upon which modern society and agriculture stands.
The Human race is only around because of evolution and the natural selection of traits.
Still to this day humans are evolving and this scientific breakthrough could be the next state of it.
Now it could be argued that using artificial trait selection in the human genome would barely be a step above Eugenics 17. But at the same time “Eugenics is a bad word, and “designer baby” is a term the media use to conjure science fiction dystopias, but is it really wrong to use new technologies to improve the human species?” (Dubrow 40). The major appeal of CRISPR-Cas 9
“lies in its possible disease-prevention capabilities.” (Sas 85). While the roots of Eugenics were sparked in racism in the United states and was the rationalization for mass genocide in Nazi
Germany, it was the notion of Eugenics upon which “[m]odern human genetic engineering entered the scientific realm” (Baird 13).
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The main problem when discussing the negatives in a biomedical or technological
innovation is that beyond the immediate negatives seen in the laboratory setting, there are so
many unknowns into the long term side effects. Recent studies have located the genetic factor for
mental traits such as intelligence, personality traits, even psychiatric risk and autism 18 and
snipping away such genes could actually leave a genetically modified individual at a
disadvantage (Kozubek). As Kozubek states in his paper, there is a section of the human genome
that fabricates a part of the immune system, known as the major histocompatibility complex, and
within this complex there are several mutations commonly associated with “human diseases,
cancer, autoimmune disease and schizophrenia” (Kozubek). Alteration of this section of DNA “
may come with a tradeoff of removing genes that are “hitchhiking” nearby and dispose an
associated risk for cancer or neuropsychiatric disorders” (Kozubek)
Many of the obstacles pointed out by Kozubek occur because DNA is not linearly
sectioned off trait by trait . Yes, there are areas that are broadly designated to an aspect of a trait
but interwoven into those areas are other genes that have been placed there through the trial and
error that is evolution. Any alteration by CRISPR-Cas 9 could lead to the disposal of these
necessary genes as well. Sure, if the gene that was displaced was one that raised the likelihood of
cancer, then great. This procedure would kill two birds with one stone. The problem is that there
is an equal chance that the displaced gene could instead contribute to personality or immune system. The more genes cut and altered the more likely it is that there will be a mistake; suddenly this seeming biogenetic cure-all turns into a game of Russian roulette 18.
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The dilemma with determining the efficacy with any controversial topic is that at the end
of the day efficacy is relative. It’s not pure science because with issues like these opinions are on
a spectrum. Some people will disagree with the idea of genetic editing for the same reason they
disagree with in vitro fertilization, because not all of the zygotes are implanted and they believe
that life begins at conception. Others will oppose genetic alteration because they are under the
belief that children born with genetic abnormalities should not be eradicated because God put
them on the planet like this and for that reason and that reason alone they should stay that way.
But only unbiased concern with the use of CRISPR-Cas 9 is that while we are one step closer to creating the perfect human race, there is no consensus on what that means or even if the technology at these point could feasibly create the “perfect” human genome without serious medical or social repercussions.
As Kozubek perfectly states, “Darwin showed us that evolution does not progress toward an ideal model or a more perfect form, but instead is a work of tinkering toward adaptation in local niches.” So before tampering with the progress that is billions of year in the making, there should be careful consideration about the ever changing “local niche.”
I have had my mind pulled both ways this entire paper. The purely analytical aspect of me was so amazed by the the biomedical advancement that my brain wanted to devour all the positive results and believe that humans could completely cure someone of a debilitating disease without any repercussions, but, unfortunately that is not the case. My fear is that if we allow an imperfect society to build up to their conceived notion of perfection that just like Icarus, our wings will melt and we will have no choice but to plummet back to Earth.
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FOOTNOTES
1. CRISPR-Cas9 is an RNA molecule made up of “20 bases of which can be designed to match any gene in
any genome, and an endonuclease (Cas9) that cuts the DNA adjacent to the CRISPR target sequence. The
cut DNA can be left in this form, inactivating the gene it is part of, or alternative DNA sequences can be
used as templates for homology directed repair or “editing” of the cut gene” (Sas 82)
2. Gattaca is a science fiction film released in 1997 that was written and directed by Andrew Niccol in which
society has become reliant on DNA testing to determine someone’s capabilities and assigns them their role
in every aspect of their life and a young man steals a genetically superiors identity in order to ascend to a
higher socioeconomic status. It is often looked to as the presenter of the theoretical problems that could
present if genetic editing became a social norm.(Gattaca)
3. Splice is a horror movie released in 2010 in which a pair of scientists go against their better judgement and
their employer’s demands to create a human and animal hybrid in secret for medical testing and things go
horribly awry (Splice).
4. Icarus is the “Son of Daedalus who dared to fly too near the sun on wings of feathers and wax. Daedalus
had been imprisoned by King Minos of Crete within the walls of his own invention, the Labyrinth. But the
great craftsman's genius would not suffer captivity. He made two pairs of wings by adhering feathers to a
wooden frame with wax. Giving one pair to his son, he cautioned him that flying too near the sun would
cause the wax to melt. But Icarus became ecstatic with the ability to fly and forgot his father's warning. The
feathers came loose and Icarus plunged to his death in the sea.” (Icarus)
5. The World Health Organization (WHO) defines Genetically Modified Organisms, or GMOs, as
“organisms (i.e. plants, animals or microorganisms) in which the genetic material (DNA) has been altered
in a way that does not occur naturally by mating and/or natural recombination.”
6. In 2000 the Inter-Ministerial Commission For Safety of Genetically Modified Organisms (CIBIOGEM)
was created to create supervise the trade, creation and usage of Genetically modified organisms. (Chan
431)
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7. Duchenne Muscular Dystrophy is genetic degenerative disease that caused by an improperly placed stop
codon on the 51st exon of the DNA chain. This genetic mishap leads to a lack of proper muscle cell
formation and causes frailty and lack of mobility within the cell.
8. A germline is the “the cellular lineage of a sexually reproducing organism from which eggs and sperm are
derived; also : the genetic material contained in this cellular lineage which can be passed to the next
generation” (Merriam Webster)
9. Mosaicism is an abnormal occurrence commonly caused by a mistake during cell division in which one
person may possess two different sets of DNA; it commonly affects skin, blood, and reproductive cells
(mosaicism).
10. Connecticut vs Griswald is a supreme court case from 1965 in which the Executive Director of Planned
Parenthood League of Connecticut, Griswald, along with the the League’s Medical Director were convicted
for the education of contraception of any kind to couples. This court ruling allowed for the privacy of
marital relations.
11. Roe vs Wade was a court case from 1973 in which a woman wished to abort her pregnancy but was unable
to have one in the state for Texas. Prior abortions could only be conducted if a medical necessity however
after brought before the Supreme Court it was deemed that women had “total autonomy” over their
pregnancies.
12. Maternal serum alpha fetoprotein measures the alpha feto protein, which is a chemical found in the liver of
a fetus; the amount of alpha fetoprotein found can determine if the fetus has conditions such as spina bifida,
Down syndrome (trisomy 21) , anencephaly, Edwards syndrome (trisomy 18), or omphalocele.
13. Newton’s Third Law of Motion is For every action there is an equal and opposite reaction.
14. Mitochondrial Replacement Therapy “uses mitochondrial DNA from a healthy donor to attempt to prevent
the transmission of mitochondrial disease from one generation to the next” (Mitochondrial Replacement
Therapy)
15. Savior siblings are “children who are born to provide HLA compatible body parts, typically umbilical cord
blood to be used for bone marrow transplantation, in order to save the life of their older sibling. They are
created using IVF so that the embryos can be screened in order to find and implant one that is a match to
the existing child.”(Is it ethical for parents to create a savior sibling?)
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16. Gregor Mendel is considered the Father of Genetics because of his scientific contribution to the discovery
of genetics. Using only scissors and a paintbrush, the monk discovered the science behind hybridization,
recessive and independent traits during his experiments from the years 1853 to 1864. (Gregor Mendel)
17. Eugenics is biogenetic philosophy in which humans are selectively bred as a means of improvement to the
human species.
18. According to Kozubek, SHANK3, DIXC1, DISC1, and C4 are considered the “most promising candidate
genes” for Schizophrenia and Autism and the variants they contain “only increase risk by a fraction of a
percentage point.”
19. Russian Roulette is a an act involving two to six people in which one bullet is put in a six cylinder rifle.
Each person holds the gun up to their head and pulls the trigger until the bullet is fired and it kills someone.
It is often used to describe instances in which an action or decision has a high probability of going
disastrously wrong.
WORKS CITED
1. Alpha-Fetoprotein (AFP) https://www.webmd.com/baby/alpha-fetoprotein-afp-in-
blood#1
2. Babineaux, Leigh “EXONDYS 51” 4 March 2017
file:///C:/Users/Leigh%20Kathryn/Downloads/Exondys%2051%20Senior%20project.pdf
3. Baird, Stephen L. "Designer Babies: Eugenics Repackaged or Consumer Options? (Cover
Story)." Technology Teacher, vol. 66, no. 7, Apr. 2007, pp. 12-16. EBSCOhost,
ezproxy.ucs.louisiana.edu:2048/login?url=http://search.ebscohost.com/login.aspx?direct=
true&AuthType=ip,cookie,uid,url&db=a9h&AN=24658576&site=eds-live.
4. Birth Defects are Costly https://www.cdc.gov/features/birthdefectscostly/index.html
5. Chan, S. and M. Medina Arellano. "Dossier" Ethics, Medicine and Genetics ": Genome
Editing and International Regulatory Challenges: Lessons from Mexico." ["The genome
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edition and the challenges posed by international regulation: lessons from Mexico"].
Ethics, Medicine and Public Health , Vol. 2, 01 July 2016, pp. 426-434. EBSCO host ,
doi: 10.1016 / j.jemep.2016.05.001.
6. Germ Line https://www.merriam-webster.com/dictionary/germ%20line
7. Gregor Mendel https://history.nih.gov/exhibits/nirenberg/hs1_mendel.htm
8. Griswald vs Connecticut https://www.oyez.org/cases/1964/496
9. Icarus http://www.mythweb.com/encyc/entries/icarus.html
10. Introduction to Eugenics http://knowgenetics.org/history-of-eugenics/
11. Is it ethical for parents to create a savior sibling? https://bioethics.georgetown.edu/2015/10/is-it-ethical-for-parents-to-create-a-savior- sibling/ 12. Johnson, Martin H. "A Moral Case Study for Discussion: Designer Babies and Tissue
Typing." Reproductive Biomedicine Online (Reproductive Healthcare Limited), vol. 9,
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13. Kczubek, Jim “CRISPR snips away risky genes—but even the bad have good in them”
12 Jan 2017 http://amp.timeinc.net/time/4626571/crispr-gene-modification-evolution
14. Mitochondrial Replacement Therapy http://www.umdf.org/mitochondrial-replacement-
therapy/
15. Mosaicism https://medlineplus.gov/ency/article/001317.htm
16. Roe vs Wade https://www.oyez.org/cases/1971/70-18
17. Sas, Daryl F. and Hannah Martin Lawrenz. "CRISPR-Cas9: The Latest Fashion in
Designer Babies." Ethics & Medicine: An International Journal of Bioethics, no. 2, 2017,
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p. 81.
EBSCOhost,ezproxy.ucs.louisiana.edu:2048/login?url=http://search.ebscohost.com/login.
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e=eds-live.
18. Spina Bifida (Myelomeningocele) https://fetus.ucsf.edu/spina-bifida
19. Splice http://www.imdb.com/title/tt1017460/
20. Tuhus-Dubrow, Rebecca. "Designer Babies and the Pro-Choice Movement." Dissent, no.
3, 2007, p. 37. EBSCOhost,
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true&AuthType=ip,cookie,uid,url&db=edspmu&AN=edspmu.S1946091007300068&site
=eds-live.