On Monday, a Chinese researcher, He Jiankui of Southern University of Science and Technology in Shenzhen, created an international sensation with his claim that he had altered the genes of a human embryo that eventually resulted in the birth of twin girls earlier this month. If proven, it would be the first instance of human offspring having been produced with specific desired attributes, using newly-developed tools of gene “editing”. In the case of the new-born Chinese babies, the genes were “edited” to ensure that they do not get infected with HIV, the virus that causes AIDS, according to the claims.
The excitement that the announcement has caused, however, is not just because of the scientific leap it represents, but more due to the serious ethical questions it raises. Gene “editing” capabilities now exist with hundreds of researchers and laboratories across the world. But leading scientists in the field, including Jennifer Doudna, the co-inventor of CRISPR technology that was used to “edit” genes in the Chinese case, have for long been calling for a “global pause” on clinical applications of the technology in human beings, till such time as internationally accepted protocols are developed.
Genes contain the bio-information that defines any individual. Physical attributes like height, skin or hair colour, more subtle features like intelligence or eyesight, susceptibility to certain diseases, and even behavioural traits can be attributed to information encoded in the genetic material. An ability to alter this information gives scientists the power to control some of these features.
Gene “editing” — sometimes expressed in related, but not always equivalent, terms like genetic modification, genetic manipulation or genetic engineering — is not new, and is widely practised in agriculture, to increase productivity or resistance to diseases, etc. But even in agriculture, genetic modification is a subject of major debate, especially in developing countries, including India. Tampering with the genetic code in human beings is even more contentious.
CRISPR (short for Clustered Regularly Interspaced Short Palindromic Repeats) technology is a relatively new, and the most efficient, tool for gene “editing” developed in the last one decade. The technology replicates a natural defence mechanism in bacteria to fight virus attacks, using a special protein called Cas9.
CRISPR-Cas9 technology behaves like a cut-and-paste mechanism on DNA strands that contain genetic information. The specific location of the genetic codes that need to be changed, or “edited”, is identified on the DNA strand, and then, using the Cas9 protein, which acts like a pair of scissors, that location is cut off from the strand. A DNA strand, when broken, has a natural tendency to repair itself. Scientists intervene during this auto-repair process, supplying the desired sequence of genetic codes that binds itself with the broken DNA strand.
From the point of view of scientists, CRISPR-Cas9 is a simple, effective, and incredibly precise technology. It is already being talked about as the technology that will revolutionise human existence in future.
The ethical dilemma
The kind of use that the technology has been put to by the Chinese researcher is something that many in the scientific community, and outside, are deeply uncomfortable with. This is for several reasons.
The technology was used to solve a problem — potential infection to HIV — that already has alternative solutions and treatments. It was not necessary to tamper with the genetic material, which can have unintended, and as yet unknown, consequences. The fact that the researcher made the announcement in the media and not in a peer-reviewed scientific journal has meant that the scientific community, as of now, has no way to verify the claims or whether the “editing” was carried out in the proper manner.
There are more serious issues as well. “The technology is extremely precise, but not 100% precise every time. There is a possibility that some other genes also get targeted. In such scenarios, unintended impacts cannot be ruled out,” said Siddharth Tiwari of the National Agri-Food Biotechnology Institute, who has used the CRISPR technology on banana genes.
Tiwari said as of now it is not clear whether regulatory approvals were taken. “In most countries of the world, possibly in China as well, such experiments are banned. In fact, in many countries it would be punishable by law. From what is known right now, we do not know whether regulatory approvals were obtained. If not, then there will be data and information gaps about the experiment.”
Then there is this highly problematic issue of trying to produce “designer” babies or human beings.
“The most promising use of the CRISPR technology is in treatment of diseases. For example, in sickle cell anaemia, a single gene mutation makes the blood sickle-shaped. This mutation can be reversed using gene editing technology. I don’t think anyone has too much reservations about such ex vivo gene therapy applications,” says Debojyoti Chakraborty of the Delhi-based Institute of Genomics and Integrative Biology who works on the CRISPR technology.
“In such cases, the genetic codes of just one individual are being changed to cure a disease. It is gene therapy. But what the Chinese researcher has done is to edit the genes of an embryo. Such a change would be passed on to the offspring. You are basically making changes in the genome of the next generation . If we allow this, nothing stops people with access to CRISPR technology to produce babies with very specific traits.” Chakraborty says.