Gene editing on a roll, but safe to clear the way?

Global scientific opinion on germline editing, a new generation of genetic engineering techniques, is that it would be irresponsible to proceed with any clinical use until safety and efficiency issues are resolved

December 13, 2015 12:46 am | Updated March 24, 2016 03:35 pm IST

Computer artwork of a DNA double helix. Photo: Science Photo Library

Computer artwork of a DNA double helix. Photo: Science Photo Library

A green translucent test tube, with a baby floating in it, greets you at the entrance of an in vitro fertilization (IVF) clinic in one of Bengaluru’s leafy neighbourhoods. Spanning two storeys of the building, it is a rather literal interpretation of the test tube baby, and perhaps also a celebration of humankind’s triumph over infertility.

Through IVF, cells from embryos are being screened for specific genetic disorders. The genetically defective ones are eliminated. In principle, you can erase an inherited genetic disorder from a single generation of family.

Anjali Thomas

The world over, laboratories have been conducting experiments and altering the genome of mice and other animals. Then, scientists in China used non-viable human embryos to modify the gene responsible for thalassaemia, an inherited blood disorder. The outcome of this experiment convinced them that it was too immature to edit human embryos. Nevertheless, there are rumours in the scientific community that similar experiments are being conducted on embryos. Using genome editing technology to reverse a defect in a human embryo, implant and then bring it to term is taboo.

“Apart from the fact that it is unethical, the problem is that the current state of technology is imprecise, and there will be unintended consequences,” says Dr. S. Ramaswamy, senior professor, Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru.

It is tempting to imagine permanently erasing of say BRAC1, the breast-cancer causing gene from the human genome. But the risk is too high. There are horrors hidden behind the banality of the term “unintended consequences”.

“We are not ready to play god,” he says.

At the heart of the debate is a powerful gene-editing technology, CRISPR-Cas9, which is relatively inexpensive, accessible and effective. Above all, it is easy to use if you have the right training. It brings the idea of designing a perfect human who is healthy and intelligent many steps closer to becoming a reality.

But even if we do develop more accurate ways to edit our DNA, we do not have the means to predict the kind of damage that we could be causing. “It’s hard to predict what will happen when we make changes in a single gene today,” says Dr. Ramaswamy.

With germline editing, the consequences will be felt for generations.

No laws in India But the recent and growing tide of voices convey a sense of urgency. Is the sound and fury justified? For India, the answer is a yes. “The current technology can have success rates of anywhere between 10 to 40 per cent or even higher. That changes germline editing from a practical impossibility to very high probability,” says neurobiologist Dr. Mitrdas Panicker, a professor at the National Centre of Biological Sciences (NCBS), Bengaluru.

There is no law stopping research laboratories and private companies from using the technology to experiment on embryos.

One of the reasons is the lack of consensus among regulatory bodies. “There is nothing stopping rogue practices and this has become a big issue,” says Dr. Ramaswamy, adding that the Drug Controller General of India is trying to use interpretations of existing laws on drugs to clamp down on improper use.

The United States has banned federal aid from being used to support germline editing while in the United Kingdom, you can apply to the regulatory body for a licence to edit the genomes of a human embryo, but only for research work. The embryos have to be destroyed within 14 days.

The guidelines in India are in keeping with international regulations, though they cannot be enforced. The ones listed by the Indian Council of Medical Research clearly state that germline editing is forbidden, says Dr. Panicker. It is in the process of being legislated.

“Editing embryonic stem cells could be very interesting for research purposes and in my view does not have the same ethical implications as editing the genome of a human embryo,” said Natalie de Souza, chief editor, Nature Methods , in an email interview.

Genomic medicine A degenerative eye disease called Retinitis pigmentosa affects one in 3,000 Indians, and is especially prevalent among families where there are consanguineous marriages. Blindness is inevitable. One of the ideas is that you take skin cells, or let’s say a blood cell, and make them stem-cell like. The technical term is induced pluripotent cells where adult cells are genetically reprogrammed to give them properties of stem-like cells. “We can engineer these stem-like cells so that they don’t carry the disease and then convert them into retinal cells. Using a scaffold — that may be generated by 3-D printing — we can generate sheets of these cells that can then be grafted into the patient through microsurgery,” says Dr. Ramaswamy, adding that this could well become a reality within two to three years.

At NCBS, Dr. Odity Mukherjee, Dr. Sanjeev Jain of the National Institute of Mental Health and Neurosciences, Dr. Panicker and their teams are also using human induced pluripotent cells to examine the Apolipoprotein-4 (APOE) gene, which is linked to Alzheimer’s disease. Using CRISPR-Cas9, they are altering alternative forms of a gene found on the same place in the chromosome, or alleles, and examining their effects on neurons generated from these cells. “We are taking blood cells from individuals out and turning them into neurons. In these experiments, we need to create aberrant neurons and control neurons and characterise them” says Dr. Panicker.

In Massachusetts, Editas Medicine, a company founded by some of the scientists who developed CRISPR-Cas 9 — there is an ongoing patent war on the technology — announced that although its focus is to correct disease-causing genes, it will use only somatic cells, or cells whose genome are not transmitted to the next generation. In August this year, it raised $120 million from Bill Gates and other industry heavyweights.

In the backdrop of calls for a ban or a moratorium on germline editing, hundreds of scientists from all over the world converged at the International Summit on Human Gene Editing, held on December 1-3, 2015, in Washington, D.C., to discuss scientific, medical, ethical, and governance issues associated with recent advances in human gene-editing research and also the the implications of this technology. After three days of debate, the summit announced that it would be irresponsible to proceed with any clinical use of germline editing until the relevant safety and efficiency issues were resolved. However, it stopped short of calling for a moratorium or a ban.

Change is coming and it is time for India to weigh in on this debate.

Corrections & Clarifications:

This article has been edited for a factual error.

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