LETTERS

Lulu and Nana open Pandora’s sequence. After all, the child will have to engineered babies? There is a need for
box far beyond Louise Brown live with the consequences. The lesson for informed reflection.
the future — proceed with care. First, the genetic technology for the
I am responding to the recent CMAJ com- The most recent dilemma in the creation of genetically engineered babies
mentary by Dr. Bartha Maria Knopper and genomic revolution was presented by the is freely available, and being used rou-
Erika Kleiderman.1 The genomics revolu- announcement (Nov.  25, 2018) that a tinely in plants and animals. Furthermore,
tion has opened Pandora’s box for all life researcher in China had genetically altered the technology has been used to treat var-
forms and continues to present chal- a gene in a human embryo that resulted in ious genetic disorders affecting different
lenges at every breakthrough. It pushes 2 babies, Lulu and Nana.3 Apparently, the tissue types, including bone marrow, mus-
the boundaries of what is possible and twins carry the disabled CCR5 gene that cle and skin, without affecting reproduc-
acceptable. For example, today, it is real- may provide them with protection against tive systems. Such practices are now com-
istic to obtain the complete DNA sequence HIV infection. They are now test subjects. monplace. The technology to undertake
(genome) of any individual. This linear Unlike the use of gene-editing protocols as these procedures is relatively easy and
sequence made up of 4  bases, adenine, therapies to correct genetic alterations in does not require expensive laboratories.
thymidine, cytosine and guanine holds the somatic cells, the gene-editing protocol In fact, it is becoming routine in many
clue to our relationships across the evolu- used to generate these twins would make research laboratories dealing with genetic
tionary tree, including interrelatedness a permanent change to the germ line that methods and almost any laboratory can
among individuals. It also provides the could be passed on to future generations. do it. The births of Lulu and Nana are not a
clues to our differences, including the The births of Lulu and Nana have scientific breakthrough. Still, it represents
risks of developing diseases. pushed the boundary of genomic revolu- a novelty and a line that has not been
The consensus among researchers, tion to include generation of genetically crossed before for many reasons.
clin­icians and other professionals is that engineered babies. This act has been Second, manipulation of embryos is
the “omics” revolution will transform life- widely condemned as premature, danger- relatively common in laboratories around
time health care and lifestyle decisions. A ous, alarming and unethical. Given this the world that deal with reproductive
global Personal Genome Project network, development, we likely will be hearing of issues. Embryos have been subject to
which currently comprises 5  active Per- an increasing number of reports on genet- extensive genetic manipulation in many
sonal Genome Projects in the United ically engineered babies in the future. Yet, animal species and modified versions of
States (Boston, since 2005), Canada another woman in China is expecting the each animal in question have been gener-
(Toronto, since 2012), United Kingdom birth of a child with genetic modifica- ated successfully. In addition, human
(London, since 2013), Austria (Vienna, tions. This is new territory. embryos are routinely handled in pro-
since 2014) and China (Shanghai, since Like it or not, this development forces grams of in vitro fertilization that operate
2017) is already underway and has begun us to ask, where do we go from here? in several countries. Genetically manipu-
to report on valuable findings. The first Although there has been a failure of self- lated human embryos have been gener-
report on the Canadian Personal Genome regulation by the scientific community, it ated, although to the best of my under-
project was published in CMAJ in 2018.2 should not lead us to stick our heads in the standing, modified human embryos have
To this end, some argue it is desirable to sand and not consider a more responsible not been implanted for further develop-
obtain the complete genome sequence of path. The outcry after this announcement ment and instead are terminated within
every newborn and use it in dealing with is natural and expected. It reminds us of 14  days. Progression of such embryos
health concerns throughout life. This the societal reaction in response to the beyond this point is banned by all
appears logical given that such individual news of the first heart transplant (1969), research ethics committees and funding
specific sequences may become a reality first recombinant DNA molecule (1972), agencies in almost all countries. I do not
for as little as $100 in the near future. Deter- first test tube baby (Louise Joy Brown, know of any exception where such a prac-
mining the complete genome sequence 1978), first genetically modified organism tice is viewed as appropriate.
will save diagnostics costs and contain the (1980) and first genetically modified organ- Third, since its inception, the clustered
most relevant information possible. ism food (1994) among others. All of these regularly interspaced short palindromic
However, on reflection, this informa- provoked societal uproar at the time, and repeats (CRISPR)/CRISPR associated pro-
tion is bound to have positive as well as brought us to new and uncomfortable ter- tein 9 (Cas-9) system (the method used to
negative connotations that will apply to ritory. Today, they are rather routine and generate Lulu and Nana) has been recog-
the life of the individual from birth to mainstream practices. To the best of my nized as having enormous potential for
death. Furthermore, the implications of understanding, they have contributed gene editing in most life forms. The tech-
this information may challenge the rights societal good and opened new economies. nology however, is still in its infancy and
of parents to give consent on behalf of The question remains, are we overreact- will require substantial research and trials
their child to generate a child’s genomic ing with the birth of the first genetically before it could be practised without any

E642 CMAJ | JUNE 10, 2019 | VOLUME 191 | ISSUE 23

LETTERS
heated in theoretical debates, with some many unknowns with the outcome that There is a need for societal discussion
comparing it to the experience with deserve reflection. For example, what do toward finding a comfortable place to draw
eugenics. Many argue that all genetic we do with off-target effects? They are a line and develop mechanisms to obey it.
modification of human embryos toward bound to happen and will generate unde- The decision should not be left for research-
production of a baby with a desired sirable effects. We do not know if Lulu or ers and scientists at the bench. It has the
genetic alteration, although possible, Nana carry any such effects. How do we potential to affect humanity and must find
must remain banned and under strict deal with the mosaics of unknown effect societal contentment. Otherwise we are left
scrutiny. This technology crosses the that will emerge during fetal develop- with this key question: Should fears of
boundary of what is acceptable today in ment? How about the effect of such a eugenics stifle scientific progress that may
society, any society. Apparently, the modification on future generations? How include avoidance of serious genetic dis-
­Chinese researcher who produced Lulu stable will it be? These questions by no eases from the family lineage?
and Nana has been fired from his posi- means represent a complete list of serious
tion. There is a need for extensive societal unknowns that must be dealt in develop- Shiva M. Singh PhD
conversations about the ethics and ing any guidelines on this technology. Distinguished university professor,
­scientific risks of the applications of this Probably the most problematic con- Department of Biology, Western
technology. cern is the question of which gene (attri- University, London, Ont.
Finally, the recent report from China, if bute) to alter? The CCR5 gene used in this
true, will be the first time genetically attempt does not meet necessary require- n Cite as: CMAJ 2019 June 10;191:E642-3.
doi: 10.1503/cmaj.71979
manipulated human embryos have been ments for alteration. 4 As discussed in
implanted and resulted in live births. The recent media coverage, 5 when polled,
genetic modification introduced in this nearly 70% of those asked would support References
case is expected to protect the children gene editing if it allowed infertile couples 1. Knoppers BM, Kleiderman E. “CRISPR babies”:
What does this mean for science and Canada?
from HIV infection. If no other changes to have children or if it allowed a couple CMAJ 2019;191:E91-2.
have resulted from the genetic manipu- to alter a serious disease-causing muta- 2. Reuter MS, Walker S, Thiruvahindrapuram B, et al.
lation (still not known), the girls will tion in an embryo. Respondents were The Personal Genome Project Canada: findings
from whole genome sequences of the inaugural
develop normally and show protection opposed to using it to enhance intelli- 56 participants. CMAJ 2018;190:E126-36.
against HIV infection not unlike vaccina- gence quotient or athletic ability, or to 3. Cyranoski D. First CRISPR babies: six questions
tion against HIV. More important, they change skin colour. Some of these attri- that remain [news article]. Nature 2018 Nov. 30.
doi: 10.1038/d41586-018-07607-3.
will transmit this trait to their children. Is butes are complex in their determinants. 4. Arenzana-Seisdedos F, Parmentier M. Genetics of
it ethically acceptable to society given They depend on genes as well as environ- resistance to HIV infection: role of co-receptors
that there are other safe and effective ment. It is easier to enhance them by and co-receptor ligands. Semin Immunol 2006;​
18:387-403.
ways to protect people from HIV that do appropriate environment, nutrition and 5. Cyranoski D, Ledford H. Genome-edited baby
not involve editing an embryo’s genes? education. The mechanisms of action of claim provokes international outcry. Nature 2018;​
The potential for gene editing in such gene–environment interactions are 563:607-8.

humans is enormous. However, the poten- not understood at present. Such traits Competing interests: None declared.

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