Lulu and Nana, faces of genetic editing in humans.
A novel form of genetic engineering could cure numerous diseases, but it also has complex technical, legal and ethical implications. It all depends on how and why it is applied.
“Two Chinese girls named Lulu and Nana came into the world crying as healthy as any other baby,” researcher He Jiankui, professor at the South China University of Science and Technology, announced on November 25, 2018 on YouTube. In the video, the scientist narrated that the girls’ pregnancy began through an in vitro fertilization procedure. He and his team obtained sperm from the father, who is infected with the human immunodeficiency virus (HIV), and eggs from the mother, who is not infected. The eggs were fertilized in the laboratory. For each fertilized egg, an egg, or zygote, of a single cell was formed, which immediately afterwards doubled into two, four, eight… until forming a blastocyst, that is, a five-day embryo, with approximately 200 cells. As a point of comparison, consider that the adult human body is made of about 37,000,000 cells. In He’s experiment, at the moment of fertilization, when the egg and sperm were united, a protein was added with instructions to modify the genetic information of the zygote, after which two of these modified embryos were implanted in the uterus of the mother. Months later Lulu and Nana were born.
To edit or not to edit
For years, scientists and philosophers had warned us about the risks of creating genetically modified human embryos with the intention of carrying a pregnancy to term, but this happened sooner than many had anticipated. In 2015, experts from around the world met at the first Human Gene Editing Summit to discuss, among other things, the possibility of genetically editing human embryos. At the end of the meeting, the organizing committee wrote a statement stating that it would be irresponsible to perform gene editing on germ cells—those that can transmit their genetic information to offspring, such as eggs and sperm—until the technique’s efficacy and safety criteria are met. were resolved and until there was a consensus on the appropriateness of the proposed application. The document ends by pointing out that until today these criteria do not exist for any clinical application. The issue of the ethics of this technology remains pending.
Gene editing consists of modifying the DNA of a cell or organism to change its characteristics. Editing the DNA chain is like editing the chain of frames that make up a film tape: you cut it in the precise place where you want to make the modification and extract a sequence, or insert a different one in its place and repeat it. stick the tape. The most common, efficient and cheap technique for editing genomes is CRISPR (pronounced “crisper”, which stands for “clustered regularly spaced short palindromic repeats”, see As you see? No. 200).
To carry out genetic editing, it is first necessary to recognize the specific region of DNA that you want to modify. However, there could be other regions in the genome with similar sequences in which, without planning, additional changes to the desired ones occur, which in some cases can have negative consequences.
GENETIC EDITING IN DNA
All organisms have genetic information stored in the DNA molecule, which is found in the nucleus and mitochondria of almost all their cells. Genetic information is written in a code consisting of four letters. These “letters” are different molecules that form the steps of the DNA double helix. Human DNA is made up of a sequence of approximately 3 billion letters. An alteration in the sequence is known as a mutation. Mutations can cause diseases that could be inherited to subsequent generations. These natural mutations can be corrected through gene editing.
Applications and warnings
On the one hand, gene editing can be used to understand the functions of human genes. For example, how embryos develop, the relationship between some diseases and genes and the evolution of diseases such as cancer and other conditions that have an important genetic component.
On the other hand, a possible clinical application is to use gene editing to cure inherited diseases caused by mutations in a single gene. Currently, more than 10,000 of these monogenic diseases are known, which affect millions of people around the world. This technology has been used to study different diseases and try to develop effective treatments, for example in HIV infection and Huntington’s neurodegenerative disease. For this, cells or organisms from non-human species, such as mice, are used.
Gene editing can be carried out in two types of cells: somatic and germ cells. Almost all cells in the body are somatic (for example, cells in the skin, liver, muscles, bones, or blood). The genetic changes made in this type of cell remain in the organism or cell in which they occurred. They are not transmitted to descendants. If unforeseen and undesirable modifications occurred in the DNA, the consequences would only affect the organism in which the change was made and would not be passed on to future generations. In germ cells it is different, since an egg fertilized by a sperm can give rise to a human being. Gene editing experiments have already been carried out on zygotes made up of between four and eight cells and on more developed embryos, which have never before been implanted to produce babies. The changes made to the DNA of eggs, sperm, zygotes or embryos will be transmitted to future generations, they will be hereditary. If genetic editing had negative consequences, these would affect the descendants.
Some countries approve the creation of human embryos for use in scientific experiments as long as the donors of the eggs and sperm are informed of the use to which their cells will be put. Some research groups use human embryos supernumerary, that is, those left over from assisted reproduction treatments (in which several embryos are created but only one or two are implanted). In some countries the use of embryos is governed by laws, so scientists are asked to justify the need and usefulness of using them. They are also asked to limit the number of embryos used and to optimize experimental protocols to use other types of cells or embryos from non-human species before applying them to humans.
Legislation regulating the use of embryos for gene editing experiments varies from country to country. In some countries like Mexico there is no law in this regard. Of course, in no country is the implantation of genetically edited embryos to give rise to a baby legally approved.
Cure deadly diseases
Gene editing has also been used in patients with diseases that are not hereditary and for which there is no treatment. This is the case of Layla, a baby who was born in June 2014 and who was detected with leukemia, a type of blood cell cancer, at three months old. White blood cells or leukocytes are a type of blood cell that normally serves to fight infectious diseases. Layla’s white blood cells were not working well due to the leukemia, so she was destined to die.
Doctors advised parents Lisa and Ashleigh to prepare for the worst and take her into hospice care. But the parents opted for a novel treatment that had not been tested in humans. It was her last option. This treatment had only been tested experimentally in mice and consisted of injecting the baby with genetically edited cells. The goal of the gene editing treatment was for Layla to develop healthy white blood cells. “It was scary to think that this treatment had never been tested in humans. But Layla was sick in a lot of pain and we had to do something,” Ashleigh said.
The cells that would be injected into Layla were white blood cells from a healthy donor modified in a laboratory. As a result of these changes, the cells acquired two fundamental characteristics that would help attack Layla’s cancer: 1) greater resistance to chemotherapy, which is so toxic that it usually kills cancer cells, but also many healthy cells, and 2) the ability to fight cancer cells. Before putting the treatment into practice, it was necessary to discuss it with the hospital’s ethics committee. Finally in 2015 doctors applied the treatment to Layla, who continued receiving chemotherapy to help eliminate the cancer cells from her. After a couple of weeks, doctors announced that the treatment was working and that the baby’s cancer cells and symptoms of the disease had been eliminated. Subsequently, to ensure that Layla had a reservoir of healthy white blood cells, she underwent a donor bone marrow transplant. Layla will likely need to use medication for the rest of her life, as well as constant monitoring of her health. In 2017 it was reported that 18 months after therapy the girl was still healthy.
Even though this treatment may sound successful, Layla’s doctors cautioned that it does not mean this technology is a suitable option for all children. However, if its effect can be replicated, it could represent an important advance in the treatment of leukemia and other types of cancer.
The great controversy
The different applications of gene editing have complex technical, legal and ethical implications. In He’s experiment, Lulu and Nana’s DNA was modified while each was still a zygote, so it is possible that the changes made to their DNA would be transmitted to their descendants, which would introduce irrevocable changes to the human species. These changes include both those made intentionally and those that may be made unintentionally.
Three days after announcing the experiment on YouTube, He made it known to the international scientific community at the Second International Human Gene Editing Summit held in Hong Kong. As a result, the organizing committee stated that two documents already existed that provide guidance on the conditions under which these techniques would be approved for use in humans for clinical purposes. For example, one of these documents mentions that clinical trials could be allowed after discussing the experiment with other colleagues and after having evaluated the benefits…