Last month, a scientific advisory group formed in the United States by the National Academy of Sciences (NAS) and the National Academy of Medicine (NAM), two independent, influential groups of scholars and professionals, backed a hugely controversial — and potentially pathbreaking — proposal to genetically modify human embryos to treat hereditary defects and disabilities. The endorsement, which came with the rider that genome editing could be permitted “only for serious conditions under stringent oversight”, puts the world’s scientific community at an ethical crossroads, even though some countries are reported to be already pursuing such research.
India, which has not squarely addressed the issue yet at the level of policy, is slated to begin a round of meetings to discuss the social and ethical dimensions of human genome editing next month.
What exactly is human genome editing?
A genome is the genetic makeup of an organism — the full set of its DNA, which is the chemical compound that contains all the information that the organism needs to function. Each molecule of DNA is made up of two strands twisted around each other. Each strand is constituted of four ‘nucleotide bases’, called A, T, G, C — and bases on the two strands pair in an A-T, G-C formation. The human genome has 3 billion of these base pairs, which reside in 23 pairs of (or a total 46) chromosomes in the nucleus of each cell. Between the years 1990 and 2003, all 23 pairs were sequenced by an international research project called the Human Genome Project.
‘Genome editing’ is the addition, removal or replacement of DNA base pairs to change an organism’s genome structure. This is commonly used in agriculture, but editing the human germline — which essentially means creating genetically modified humans through the the manipulation of their genes — is an altogether different ball game, and is specifically prohibited in over 30 countries. While germline editing is focussed on editing the genes — or traits — that pass on from parents to children, it runs the risk of affecting even non-targetted genes.
What techniques are available for genome editing?
In recent years, a technique known as CRISPR-Cas9 has provided a new dimension to genome editing. It is faster, cheaper and more accurate than earlier techniques, and can precisely target a sequence of DNA, extract, edit or replace it even in the embryo stage. The technique can prevent hereditary diseases such as sickle cell, thalassaemia, HIV, cancer, and Huntington’s disease from passing on to children.
Another popular method is Somatic Cell Gene Therapy (SCGT) which affects only an individual and not his or her future generations. The technique targets a group of cells, and can be used clinically to treat diseases such as thalassaemia and haemophilia that are single gene disorders. Research and clinical trials are currently ongoing.
What does the American panel say on human genome editing?
A 22-member international committee of researchers, lawyers and ethicists have come out with a 261 page report on Human Gene Editing: Scientific, Medical and Ethical Consideration that encourages research in human germline editing but only to correct disabilities and hereditary defects, and not for “human enhancement” — that is, to build up traits and capacities such as physical strength, or to improve intelligence. “While it could be used to treat muscular dystrophy, genes could also be manipulated to get muscles enhanced for sports. There is a very thin line there,” said Richard Hynes, cancer researcher at Massachussets Institute of Technology, and a member of the committee.
The report has also called for public discussion and accessibility for both rich and poor before gates are thrown open for genome editing. It has recommended genome editing only in cases where no other “reasonable alternative” is available. Gary Merchant, professor of Law at Arizona State University and another member, said a standard set of guidelines to command ethics in genome editing must be put together by various countries.
Where does India stand on this matter?
India has not permitted trials of CRISPR-Cas9 technology to edit the human germline. The Department of Biotechnology and Indian Council of Medical Research (ICMR) will meet with Inserm, the French National Institute of Health and Medical Research, in April to discuss the social and ethical implications of genome editing in India, after which the government plans to issue broad guidelines for researchers.
“Our main concern is that this technology should not be used for human enhancement,” ICMR Director General Dr Soumya Swaminathan said. Meanwhile, several countries, including the US, UK, China and a few European countries will meet in China later this year to take forward discussions on genome editing. There is no clarity yet on India’s participation.
Nobel Prize winning biochemist Dr Venkatraman ‘Venki’ Ramakrishnan, president of London’s Royal Society, said India has a long way to go before it can consider germline editing. “The technology they (India) need to develop will be first used to correct defects in somatic cells. Germline correction is distant future for India,” he has said.
According to Professor Merchant, ethical concerns are “a little more (important) in India (than in many other countries), but strict laws can help regulate it”. Prenatal sex determination was banned by The Pre-Conception and Pre-Natal Diagnostic Techniques (PCPNDT) Act, 1994, and The Surrogacy (Regulation) Bill, 2016, which has been introduced in Parliament, seeks to prohibit commercial surrogacy — in India’s ethical-legal environment, germline editing is unlikely to have easy passage. The technology can be used by the rich to ‘customise’ a baby with desired traits, and allowing human genome editing could make India a hub for a certain kind of medical tourism, rather like surrogacy has done, experts point out.
“The concept of gene editing can slip into prenatal testing, foetal management and IVF. Developing and underdeveloped countries that face social barriers such as preference for male children need to tread carefully,” said Josephine Johnston, research director at The Hastings Center, the world’s first bioethics research institute.
What is the situation in other countries?
In 2015 in London, 16-month-old Layla Richards became the first-ever recipient of gene therapy to cure her of ‘incurable’ leukaemia. A 11-month-old baby was also treated subsequently for the same cancer using gene editing technology. The UK has moved fast on research and clinical use of CRISPR-Cas9, and the NAS-NAM paper has encouraged cautious research in the US. In Germany, where strict laws exists for assisted reproduction, research in the human embryo is restricted. Austria, Italy, Spain and the Netherlands have banned human germline editing, while ambiguous guidelines are in place in Mexico, Canada and Argentina.