Editorial 1 : Jumping genes and RNA bridges promise to shake up biomedicine
Introduction
Barbara McClintock at the Carnegie Institution found that some genes were able to move around within the genome. These genes were called mobile elements or transposons.
Prof. McClintock’s observation
- She also made another significant observation: depending on where the mobile elements were inserted, they had the ability to reversibly alter gene expression.
- She used corn kernels’ colours as a surrogate to understand hereditary characteristics, and in this way figured out transposons moved about in the genome of the maize plant.
- She was awarded the Nobel Prize in Physiology or Medicine in 1983 for this work.
- Between 1948 and 1983, researchers found transposons in an array of life-forms, including bacteriophages, bacteria, plants, worms, fruit flies, mosquitos, mice, and humans. They were nicknamed ‘jumping genes’.
‘Sleeping beauty’ transposon
- The discovery of transposons revolutionised our understanding of genetics, in particular their role in enabling nature’s wondrous diversity.
- Transposons influence the effects of genes by turning “on” or “off” their expression using a variety of epigenetic mechanisms.
- They are thus rightly called the tools of evolution, for their ability to rearrange the genome and introduce changes.
- More than 45% of the human genome consists of transposable elements. Just as they create diversity, they also create mutations in genes and lead to diseases.
- However, most of the transposons have themselves inherited mutations and have become inactive, and thus can’t move around within the genome.
- Over the years, researchers have attempted to resurrect inactive transposons from the genomes of the animal kingdom, hoping that the results will be useful in biomedical applications like genetic correction to cure a disease or for gene therapy.
- For example, in 1997, researchers studied the genomes of fish and reconstructed a transposon called “sleeping beauty” at the molecular level.
- This transposon became dormant in vertebrates millions of years ago. The researchers elegantly reprogrammed the synthetic avatar to work in human cells.
RNA-guided transposons
- On June 26, Nature published a paper describing a new RNA-guided gene editing system.
- This tool builds on an older discovery: that one of the genes in the IS110 family of bacterial transposons contains the instructions for cells to make an RNA molecule with two loops.
- Scientists found this RNA could bind to two pieces of DNA, rather than the usual one piece, and form a bridge between them. This is a very useful ability.
- In the new study, the researchers used the bridge RNA to edit the DNA. The two loops of the RNA can independently bind to two separate pieces of DNA.
- One of the loops identifies the target site in the genome that needs to be altered. The other loop specifies the DNA to be inserted in its place.
- Each loop is independently programmable, which means researchers can mix and match any target and donor DNA sequences of interest.
- In their paper, they reported that in Escherichia coli bacteria, the bridge RNA had more than 60% insertion efficiency (i.e. ability to introduce a desired gene) and a 94% specificity (ability to target the intended location on the genome).
Boon for synthetic biology
- Researchers from the University of Tokyo described the structural and molecular mechanisms of genome modification guided by bridge RNA.
- The researchers used cryo-electron microscopy to study the IS110 transposons.
- They found that it works as a dimer — a complex compound formed by bonding two copies of a simpler compound.
- One copy binds to the target DNA and the other binds to the donor DNA, bridged by the bridge RNA.
- This alternative form of genome-editing has many advantages.
- CRISPR-mediated editing sometimes leaves small bits of nucleotides added/deleted during the repair process.
- DNA recombination mediated by bridge RNA on the other hand makes a clean cut, making the edit specific and tidy.
- Equally importantly, the latter can facilitate the addition, deletion or inversion of DNA sequences of virtually any length.
- Researchers can exploit this feature by inserting any desirable genetic cargo — such as a functional copy of a faulty, disease-causing gene — into any location on a genome.
Conclusion
Such an ability spells a big boon for synthetic biology, where entire sets of genes need to be inserted or removed from organisms. Similarly, the technique can be used to manage, or even treat, a wide variety of genetic diseases: a functional copy of a gene can be replaced in a given genomic location. Researchers may also be able to treat chromosomal inversions or deletions, which are currently beyond the reach of any of the editing tools we have.
Editorial 2 : A law around low-carbon climate resilient development
Context
In a landmark judgment, the Supreme Court of India recently recognised a right to be “free from the adverse impacts of climate change” in M.K. Ranjitsinh and Others vs Union of India — sourcing it from the right to life and the right to equality.
Law to inform development choices
- Preparing India to reduce the risks of climate change and address its impacts requires nothing less than re-orienting development toward low-carbon and climate resilient futures.
- Any law that attempts to take this on must ensure these objectives are internalised in routine decision-making at all levels of development.
- Because climate change relentlessly targets the vulnerable, and because an energy transition must be just, it must be grounded in the imperative of advancing social justice.
- While the concept of climate law is often associated with a top-down approach of setting and achieving targets, in a developing country, this approach is limited because addressing climate change is about more than limiting emissions.
- Instead, it requires careful, ongoing, consideration of each developmental choice and its long-run synergies and tradeoffs with low-carbon and climate resilient futures.
- To achieve this, the substantive right of protection against adverse effects of climate change must be realised, in part, through well-defined procedures in law that are applicable across levels of government.
- Climate action is more credible when a well-designed institutional structure is strategising, prioritising, troubleshooting and evaluating policies behind the scenes.
- Umbrella laws that define government-wide goals and substantiate them with a set of processes and accountability measures are a known and increasingly popular way of bringing climate action to the heart of government.
- However, these laws vary, and India’s approach must be tailored to our context. Starting from a low base of per capita emissions — less than half the global average — India’s emissions are still growing, and our objective should be to squeeze out as much development as possible from each ton of carbon and avoid locking-in to high carbon futures.
- Moreover, India is highly vulnerable to climate impacts, and climate resilience must be an essential element of the new law. In meeting both objectives, considerations of social equity must be central.
- Consequently, India’s law must ensure development, but in a low-carbon direction while building resilience to ever more pervasive climate impacts.
- What we arrive at, then, is a law that helps navigate developmental choices. It must create the basis for thoughtful decision-making toward achieving a low-carbon, resilient society.
Have a low carbon development body
- A framework climate law should lay out an institutional structure capable of crafting viable answers to these questions.
- An independent ‘low-carbon development commission’, staffed with experts and technical staff, could offer both national and State governments practical ways of achieving low-carbon growth and resilience.
- This body could also serve as a platform for deliberative decision-making.
- Vulnerable communities and those that may lose from technological change need to be systematically consulted.
- Hearing their concerns and incorporating some of their ideas could lead to longer-lasting policy outcomes.
- An example is South Africa’s Presidential Climate Commission, which is tasked with charting a course toward just transition based on inputs and representations from stakeholders.
- Accordingly, the law could create a high-level strategic body, which we label a ‘climate cabinet’, a core group of Ministers plus representation from Chief Ministers of States, tasked with driving strategy through government.
- A whole-of-government approach will also require dedicated coordination mechanisms for implementation.
- The Ministry of Environment, Forest and Climate Change should continue to play a central role, but it needs to be complemented by higher-level coordination.
- Here, the pre-existing Executive Committee on Climate Change (made up of senior bureaucrats from multiple Ministries), provides a useful template but only if it is reinvigorated with clearly specified legal powers and duties.
Engagement with the federal structure
- Not least, the law must pay attention to India’s federal structure. Many areas crucial to reducing emissions and improving resilience — electricity, agriculture, water, health and soil — are wholly or partially the preserve of State and local governments. When a climate impact is felt, it is felt first, and most viscerally, at local levels.
- First, the law must establish a channel for subnational governments to access national scientific capacity, potentially through the low-carbon development commission as an intermediary, as a step toward solving the pervasive problem of insufficient local climate scientific capacity.
- Second, it could articulate ways of financing local action, for example by requiring centrally-sponsored schemes to be more aligned with climate goals or by requiring national departments to climate tag expenditure towards local climate resilience.
- Third, the law could establish coordination mechanisms that allow the Centre and States to consult on major climate decisions.
- To enable development of State-specific solutions, States could also build complementary institutions to those at the Centre, providing knowledge, strategy-setting, deliberation and coordination functions.
Conclusion
The Court’s historical pronouncement in M.K. Ranjitsinh opens the door to legal and governance changes that make possible an actionable right against the adverse effects of climate change. But to realise this promise, this open door has to actually be used to pass a climate law that is well suited to the Indian context, that steers Indian development choices toward a low-carbon and climate resilient future, and that also advances justice.
