The zygote travels to the uterus and attaches to the inner wall of the uterus and grows into a baby.
If we are able to redress most intractable ailments through tech breakthroughs, why not? Less than a century ago, antibiotics were not the normal cure. But it revolutionised the treatment of infections and proved to be the lifesaver.
Making a baby the natural way starts with the sperm getting deposited in the vagina during sexual intercourse, the sperm finding its way to eggs and ending in the fusion of one sperm with the egg to produce a zygote. The zygote travels to the uterus and attaches to the inner wall of the uterus and grows into a baby. Though all these events seem to be simple, having a baby produced this way is not possible in the case of 12-28 per cent of the people of reproductive age trying to have a baby. Reasons could range from the mere inability of the male to deposit sperms in the vagina to extremely complex situations where embryo formation is impaired or embryo fails to attach and survive in the uterus.
John Rock, a 1918 graduate of Harvard University Medical School, was the first to extract intact a fertilised egg in 1953. In 1959, Min Chueh Chang at Worcester Foundation for Biomedical Research made a seminal discovery. He collected sperm and egg from rabbits, fused them in a laboratory dish (called in vitro fertilisation or IVF) and transferred it to the uterus, resulting in the birth of a rabbit. Similar protocols were attempted in human beings by scientists in the early to mid-’70s, though these pregnancies did not result in live births.
Landrum Brewer Shettles attempted to perform an IVF in 1973, but his departmental chairman interdicted the procedure at the last moment. Though an attempt by Patrick Steptoe and Robert Edwards in 1976 resulted in an ectopic (outside uterus) pregnancy, they ultimately successfully carried out a pioneering conception in 1977 which resulted in the birth of the world’s first baby to be conceived by IVF, Louise Brown, on July 25, 1978, at Oldham General Hospital, Greater Manchester, UK.
Subash Mukhopadyaya, a physician from Kolkata produced a test-tube baby, later named as “Durga” (alias Kanupriya Agarwal), born on October 3, 1978. However, state authorities prevented him from presenting his work at scientific conferences. His work was not recognised by the Indian and international scientific community. Dejected, he committed suicide on June 19, 1981. Robert Edwards was fortunate to live to receive the Nobel Prize in physiology and medicine in 2010 at the age of 80. He died on April 10, 2013.
Today, a broad spectrum of Assisted Reproductive Technologies (ART) has given hopes to millions of infertile couples to have babies. Since 1978, more than eight million babies have been born through IVF. This powerful technology raises the chance of producing babies who would never have been born otherwise.
If infertility is nature’s deliberate way to eliminate the defective gene pool from circulation, IVF introduces a chance to forcefully keep it in circulation. We could consider infertility-causing defects in genes as an example. The carriers of such defects will not normally produce a child, and this defective genome will be erased from the population for ever as the carrier is rendered infertile. Creating a child from such a parent through IVF, knowing that the child would have the defect present in either/both of the parents is not a safe practice.
Manipulating genes in the zygote (fertilised egg) has been used extensively in creating knock-in (inserting a gene), knockout (deleting a gene) and knockdown (reducing the expression of a gene) animal and plant models for research purposes. The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans, and Oliver Smithies in 1989, for which they were awarded the 2007 Nobel Prize. Today, there are thousands of animals and plants available which are all created for understanding the functions of specific genes. About 15 per cent of such manipulations are lethal — which means that the genetically modified organism will not survive.
Here comes the possibility of correcting an error in a genome with the purpose of producing a child who will not inherit the error in question. This can be done through gene editing, wherein the part of the gene where the error is present is overwritten — just like deleting a few letters from a wrong word in a sentence and retyping it correctly. There are various techniques available for doing this task. Today, four families of engineered nucleases are being used for this purpose, which include mega nucleases, zinc finger nucleases (ZFNs), transcription activator-like effector-based nucleases (TALEN), and the clustered regularly interspaced short palindromic repeats (CRISPR/ Cas9) system.
CRISPR-Cas9 system is the newest gene-editing tool and is said to have been used by Hi Jiankui from the Department of Biology of the Southern University of Science and Technology in Shenzhen, China, to create the first human genetically edited babies, twin girls known by their pseudonyms, Lulu and Nana. He edited the human gene coding for a protein called CCR5, which is used by the AIDS virus to enter human cells and infect human beings. He introduced a mutation known as CCR5?32 in this gene in these babies, which in my opinion, is to prove the point that gene editing in human early embryos is possible to introduce a desired trait in the baby. In fact, some people bear CCR5?32 mutation naturally and are resistant to HIV infection.
Several technologies have scared the world — possibly for senseless reasons. Trains, telephones, TV, CRT monitors, Wi-Fi, Y2K bug, robots, cloning, cassette recorders, VHR recorders, video gaming and internet are some of the examples. No doubt that gene editing is a very powerful tool, and the precision with which the manipulation is done is a matter of concern for many who are aware of the technicalities of the procedure. While CRISPR-Cas9 system is highly specific, the specificity has been improved recently by Ryan and colleagues (Nucleic Acids Res. 46(2): 792-803).
Gene manipulation in animals or plants for research purposes has not created any monstrous creature so far, though it is true that such manipulations are done in contained environment. Precise and targeted gene editing will help us eradicate heritable diseases. We have substantial knowledge about the link between genes and diseases, and this knowledge base is fast expanding. So let us think about the responsible use of gene editing tools for the benefit of mankind, rather than crying foul about the technology. As is true with any other revolutionary technology, gene editing does have the bad side, which can be easily dealt with by formulating appropriate guidelines.
(The author is a senior scientist at the Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram. Views expressed are personal and may not be endorsed by RGCB or Department of Biotechnology,New Delhi.)
Genetic parenting: ‘designer babies’
The first “designer baby”, whose birth in America made international headlines, has rekindled furious debate about the ethical issues of using genetics to select the attributes of babies. Genetic screening was used so that the test-tube baby Adam Nash could become a donor for his six-year-old sister Molly, who has a rare and fatal genetic disease. But whilst the case has inspired sympathy, it has also increased fears of babies becoming “commodities” where intelligence and athletic prowess are bought. The genetic Pandora’s box is open. Mark Oliver guides you through the ethical minefield.
What is a ‘designer baby’?
Adam Nash is the world’s first known designer baby. Using a revolutionary new technique, called a “pre-implantation process”, scientists genetically selected his embryo so that he would have the right cells to save the life of his dying sister. His parents, Lisa and Jack, were able to conceive normally but their sperm and eggs were manipulated in a laboratory to create 15 embryos. One was selected which did not have Fanconi’s anaemia, which their daughter Molly suffers from. Normally, there would be a very high chance any baby they had would also have the disease. After Adam’s birth last month, he became a donor to his sister and there was a blood transfusion which has more than doubled her survival chances.
If he saves his sister’s life, why the concern?
For many the specifics of the Nash case lie outside the main ethical issues. However, despite sympathy for the parents’ dilemma, there are those who believe it is intrinsically wrong to bring a human being into the world for any purpose other than living their own life. But, in the main, fears revolve around the precedent this birth sets and that the technique could be extended to allow parents to “design” children with a variety of genetic traits.
What would be available to parents deciding to have a ‘designer baby’?
Eye colour, athletic ability, beauty, intelligence, height, stopping a propensity towards obesity, guarante-eing freedom from certain mental and physical illnesses, all of these could in the future be determined by genetic science. Even characteristics such as sexuality could be selected. The problem for many is that the frontiers of what is now genetically possible are being pushed back far quicker than the ethical debate can keep up with. In Britain, the Human Fertilisation and Embryology Authority has not even finished its public consultation about the pros and cons of pre-implantation genetic screening, and the debate has already rushed on.
Who are the people worried about genetics?
Some scientists have voiced concerns although many echo the views of Dr John Wagner, of the University of Minnesota, who carried out the Nash operation. He said he was not an ethicist and was just trying to save the girl’s life. The anti-abortion charity Life said selecting top quality embryos was more akin to the farmyard and that one child should not be used to save the life of another. The Catholic Church has condemned any tampering with genetics, even in cases such as the Nash’s. Groups worried about social injustices, and the gap between rich and poor, are also concerned at a future where the wealthy can purchase a perfect offspring. Last year, related controversy was created when a US entrepreneur started a website offering the embryos of models.
(Courtesy The Guardian)