On November 25, Jiankui He, a professor from the South University of Science and Technology of China, released a video on YouTube announcing the birth of twin girls he claimed to have performed ‘gene surgery’ on to prevent HIV infection. The news exploded on media with comments of disbelief, censure and some cautious appreciation from the scientific community as well as the public.

So, what is ‘gene surgery’ and what is the controversy all about?

We carry, in each of our trillions of cells, a copy of the human genome. The genome is made of DNA, a very long polymer made of pairs of four chemical building blocks (denoted by the letters A, T, G and C). It is this very precise sequence of A, T, G and C, all 3 billion pairs of them that we call the human genome. Changes in this sequence lead to the interesting differences between each of us.  But, these changes also may result in mutations that cause diseases. These changes in the DNA sequence happen as DNA is copied again and again in the course of evolution. Many of these changes are lost in the mists of time as nature selects the most adaptable individuals, but rare changes survive through generations.

Human beings have been experimenting with DNA since its discovery in 1869 by Friedrich Miescher. We have learnt that changes made will be passed on as cells replicate their DNA every time they divide. We have long figured out how to make changes in the DNA in the test tube. We now routinely introduce new DNA into bacteria with technology now known as recombinant DNA technology. We have made numerous changes to bacteria so they can produce hormones, growth factors and other proteins for human use.

We have introduced new DNA into crop plants to protect them from pests, droughts or to increase their nutritional value. These genetically modified organisms continue to be controversial, but have been adopted in many parts of the world, including India.

In the past 20-25 years, a number of clinical trials in patients have shown promise for the use of gene therapy for treatment of incurable diseases. Gene therapy currently involves the introduction of genes into patients with non-functional copies of the same genes such as in the case of patients who lack the Adenosine Deaminase gene due to which they suffer from Severe Combined Immunodeficiency (ADA-SCID).

Complex organisms, including humans, have a sophisticated immune system that protects the body from infectious agents such as bacteria and viruses. The adaptive immune system is highly versatile and retains the memory of previous infections to respond more efficiently and strongly against a second infection by the same species, a property that is utilised very efficiently in vaccinations.

Until a decade ago, bacteria were not thought to have any such ability. But bacteria turned out to be smarter than we thought. In 1987, it was discovered that bacterial genome contains bits and pieces of DNA from viruses that came to be known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). By late 2000s, it became clear that bacteria were storing these snippets of DNA from viruses as a memory of a previous attack. The next time the same virus infects, the bacteria is now armed with DNA chewing enzymes (CRISPR associated or Cas proteins) that cut the viral DNA down and thus prevent infection. This in itself was a great discovery.

As often happens in science, this intriguing fundamental discovery soon led scientists to wonder if the bacterial protein, Cas, could be trained to cut any piece of DNA you provide in the guise of a virus! Since then, there has been an explosion of research on CRISPR-Cas systems to develop better and smarter ways in which specific regions in DNA could be cut, modified or removed from cells, animals and human stem cells.

The myriad possible applications of such a system made it also a very lucrative business concept. The financial implications of such a technology resulted in a hotly contested three-year patent war between the Broad Institute of MIT, Harvard in Cambridge, Massachusetts, and the University of Berkeley, California, which the US courts finally awarded to the Broad Institute.

The very simplicity and elegance of the CRISPR-Cas systems have made it possible for us to dream of making changes in the genome of human beings for beneficial purposes. But, the major technological challenge to this system remains in its fidelity. In other words, although the Cas protein is designed to cut one site on the DNA, it often makes mistakes and cuts in other places in the genome. This can lead to changes in other places in the genome, with undesired side effects. This is a danger, especially when working with humans.

Jiankui He shot to fame in November as the first person to make a change in the genome of a human embryo that was allowed to be born. Now, there are two babies, known to the world as Lulu and Nana, whose DNA have been engineered to remove a protein known to help in HIV infection. The intended consequence is to protect the babies from acquiring the HIV infection from their father, who is HIV positive. But where else has the Cas protein cut their DNA? Jiankui He says, nowhere else.

Scientifically, this is the claim currently up for scrutiny. Ethically, as a society, we brace for questions of unintended consequences, in case our experiments falter. On the other hand, we can also look back and see that many new revolutionary changes happened by foolhardy jumps into uncertainty by individuals.

We humans have not yet managed to create life, as we had long aspired to do. But today, we hold the key to editing life. But do we even want to do it? What and how should we ensure we do not err? How, or can we even stop Dr Frankensteins from entering the playground?

Chetana Sachidanandan is a senior scientist at CSIR-Institute of Genomics & Integrative Biology, New Delhi. The views expressed here are personal.