Evolutionary engineer Kevin Esvelt, at the Massachusetts Institute of Technology in Cambridge, works with gene drives, engineered bits of DNA that can cause a mutation to become heritable all the time. He calls for researchers to create and use safe lab procedures while working with this powerful but potentially risky technology.

What is a gene drive?

In nature, a gene drive occurs when a DNA sequence spreads through a population by breaking the conventional rules of inheritance. For example, if an organism has a single copy of a fluorescent marker gene and its mate has none, normally only half their offspring will fluoresce. When a gene-drive system is in play, almost all of them will glow.

How can scientists use this capability?

Gene drives allow us to drive altered traits through wild populations over generations. For instance, we could alter the DNA of wild mosquitoes to stop them from carrying disease. We could restore damaged ecosystems and save endangered wildlife by genetically removing invasive species.

How did your insights help to propel this field?

Even ten years ago, heritable genome editing was a possibility, but no one had found a molecular tool that would enable it to be done efficiently. In 2013, laboratories began using CRISPR to precisely edit the genomes of many species. I realized then that this tool could be used to build stable gene drives in many complex organisms. It could also be used to build reverse drives, which are like molecular erasers for overwriting previous edits.

Why did you explain how gene drives would work before you published results showing that they could work in any organism?

Most advances don’t give individual scientists the power to affect entire ecosystems. By detailing what was possible, how it could be achieved and what safeguards were needed to prevent any accidental release of altered organisms from the lab, we hoped to set an example of how future work in gene drives should proceed.

Why was this important?

A single escaped organism that found a mate could eventually alter most of the local population and, very possibly, every population of that species worldwide. The ecological risk might be low, but the damage to public trust in biotechnology could imperil the future of the field.

Did you want researchers to agree on some guidelines first?

My immediate priority was to prevent the accidental release of any gene-drive organisms into the wild. I wrote to the few researchers working on gene drives to explain my concerns about ethics and safety. Not all of them responded.

Then, what happened?

Last year, when we released results showing that gene drives work in yeast. Then another group — who were working with fruit flies — independently created a functional gene-drive system. They were careful to keep the flies contained, but unlike our paper, their manuscript, which was meant to be published as a how-to for other labs, made no mention of safeguards or the risk to wild populations. We got wind of that and approached them. To their credit, they agreed to include those details.

Did your efforts help to usher in regulation?

The fruit-fly case triggered responses from many scientists. For months, we struggled to agree on which safeguards should be used in the lab. We eventually published our recommendations in July 2015, and this year the US National Academy of Sciences released a report setting out how to conduct gene-drive research responsibly.

Should gene-drive information be classified?

Classifying such information would hinder beneficial applications and threaten biosecurity. We must know which species to monitor. Open science is the best defence and the best way to earn public support.

Read here. html. PDF

Mice Against Ticks

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Also seen in the picture is Dr. Asim Sil, an ophthalmologist who practices in the area. He hosted Sinha’s visit. The little girl had a tragic history. Extreme poverty forced her parents to abandon her. Due to this neglect and her blindness, she met with an accident in which she lost both her legs below the knee. At the time the picture was taken, she was living with her grandmother (the woman in the yellow sari) who herself was desperately poor. This visit helped crystallize in the professor’s mind the potential humanitarian and scientific significance of the effort that would eventually become Project Prakash.

Pawan Sinha, whose work among visually impaired children in India received a U. S. Presidential award in 2012, talks to Vijaysree Venkatraman about a mission that seamlessly blends research with a humanitarian cause. Sinha is a researcher at the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology.

Q. What is Project Prakash?

A.  Project Prakash grew from the confluence of a humanitarian mission and a fundamental scientific quest. The mission is to bring light into the lives of curably blind children and, in so doing, answer some fundamental scientific questions about how the brain develops and learns to see.

Q. You are based in Boston. But the work is done in India, correct?

A. India is home to one of the world’s largest populations of blind children. Nearly 400,000 children in the country are either blind or severely visually impaired. The visual handicap, coupled with extreme poverty greatly compromises the children’s quality of life; childhood mortality rates are greatly elevated and prospects for education are severely diminished. Project Prakash seeks to identify and treat blind children, and simultaneously, build awareness amidst the rural populace regarding treatable and preventable blindness.

It also provides us an opportunity to study one of the deepest scientific questions: How does the brain learn to extract meaning from sensory information? The researchers have begun following the development of visual skills in these unique children to gain insights into fundamental questions regarding object learning and brain plasticity. This is a unique window into some fundamental mysteries of how the brain learns to extract meaning from the world. The humanitarian initiatives are creating a population of children across a wide age-range setting out to learn how to see.

Q. How do you find candidates for treatment?

A. Outreach is perhaps the most logistically complex and challenging aspect of Project Prakash. We have provided surgical treatments to 448 children, and non-surgical care to 1400. To identify these children, we had to screen over 40,000 children in many states of India.

We realized early on that we simply couldn’t expect children needing treatment to show up on their own at the hospital in New Delhi. Many of them and their parents do not even know that their conditions are treatable. The parents often ascribe their child’s blindness to bad karma – inviolable cosmic justice for bad deeds in a previous life. Faced with these preconceptions, we understood that we had to be proactive. We would need to go out into the villages to find children who were curably blind.

So we organize ophthalmic screening sessions in villages and small towns. A few weeks before our team’s visit, we send word to villages about the ‘eye camp’ and encourage them to bring all children with visual problems for a free check-up. On the day of the session, a team of primary health-care workers and optometrists sets up a simple screening station in the village and does eye check-ups of tens, sometimes hundreds, of children. These sessions allow us to identify curably blind children and also those whom we can help non-surgically (such as children with eye infections than can be dangerous if left untreated, or those with uncorrected refractive errors). The candidates for surgery come to New Delhi for a more thorough ophthalmic examination and, if there are no counter-indications, then the child is given a date for surgery.

All expenses of surgery and transport are borne by Project Prakash.

Q. What are some scientific insights you have gathered thus far?

A. One of the potentially far-reaching results is evidence of recovery even after prolonged congenital blindness. These findings argue for a reconsideration of some long held conceptions regarding brain plasticity and time-lines of learning.

Having followed the post-operative development of several children, my students and I have found that while some aspects of vision, such as acuity, are compromised by a history of deprivation, there is evidence of skill acquisition on a variety of functional vision tasks ranging from simple shape matching to object and face recognition.

The human brain, these findings suggest, retains an ability to launch programmes of visual learning well after the normal period of their deployment has passed. These results have significance for basic neuroscience as well as the practice of paediatric ophthalmology and the implementation of late stage blindness treatment programmes.

Q. What lies ahead for Project Prakash?

A. Sociological aspects of the work guide the evolution of the project. I would never have, for instance, expected that parents might actually prefer to have their child remain blind just so that they can stay enrolled in a school for the blind that gives them free food and clothes. Yet, the level of poverty in some households is so extreme that this happens.

Another surprise for us has been the difficulty Project Prakash children have encountered in entering the educational mainstream despite having sight. But, their age (too old to be enrolled in grade 1) often keeps them from starting their educational journey. This is indeed a tragedy and one that we are working towards addressing. Moving forward, we want to add an educational component to the medical and scientific missions of Project Prakash. We intend to do so by providing a ‘compressed’ educational course to the children to bring them up to an age-appropriate level so that they can then enter the regular educational stream.

The challenge that we have to meet in the coming years is to accomplish a seamless integration between medicine, research and education, at a scale many times that of our current operations. A good way forward is to set up an integrated campus with a pediatric hospital, a school and a research facility.

The key need to realize this dream is funding. Our estimate for the center is $20 million. This seems like a daunting figure, but considering the multifaceted impact it can have on thousands of children, it is a small sum.

More about Project Prakash.

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Abha Sur is part of the humanities faculty at the Massachusetts Institute of Technology. A physical chemist by training, she taught this subject and also published several papers on laser spectroscopy, her field of specialization. Then, the focus of her research shifted, taking her from the lab bench to the library archives. She wanted to find out more about the life and times of India’s first Nobel Laureate.

Sir C. V. Raman’s (1888- 1970) name is immortalized in science because he demonstrated the molecular scattering of light – a phenomenon now known as the “Raman Effect.” When he won the Nobel Prize in 1930, India was still under British rule. Immediately after, he assumed the directorship of the Indian Institute of Science. In Independent India, Raman established a premier institute of research. Sur’s critical analysis of the larger effect Raman had on the nation’s science and scientists has taken the form of the book: Dispersed Radiance: Caste, Gender, and Modern Science in India. (New Delhi: Navayana, 2011).

Read the entire interview here. html. pdf

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Q Why is it so important to study life in the treetops?
A Forest canopies are the interface between atmosphere and earth — a critical place essential for life on earth. Also, canopies contain almost half of our land-based biodiversity — a huge genetic library of species — and are the source for many important services that provide life on earth: energy production from sunlight, hotspot for fruits and flowers, gas exchange, carbon storage, homes for millions of creatures, and climate control! We need to understand forests — especially, their canopies — because humans cannot live without trees.

Read the rest of the interview. html. Nature-IndiaTreetop

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Snakebite, a recent inclusion to the list of neglected tropical diseases drawn up by the World Health Organization, could be the most neglected of all neglected tropical diseases in the 21st century, says David Warrell, Emeritus Professor of Tropical Medicine at the University of Oxford.

India has long been considered as the nation with high incidence of snakebites, but the full extent of this public health problem remained unknown. Published data from the late 19th and early 20th centuries suggested that the annual snakebite mortality in India was about 20,000, says Warrell. More recently from 2004 to 2009, the Government of India’s Central Bureau of Health Intelligence website reported an average of only 1,351 snakebite deaths each year. “It was clear from these disparities that official data grossly underestimated the size of the problem,” he adds.

A recent report in PLoS Neglected Tropical Diseases, co-authored by Warrell, confirms that there is a systemic under-reporting of snakebites. The findings from a national mortality survey in India, the Million Death Study, indicates that close to 46,000 people in the country die of snakebites every year, as opposed to the estimated 2000.

Because rural victims of snakebite rarely seek medical help from hospitals, researchers dispatched fieldworkers to conduct interviews with relatives and neighbors of the deceased. Being bitten by a snake is a sufficiently dramatic event, so people vividly recall details, Warrell had stated in an editorial in the National Medical Journal of India. Such recollection helps physicians decide the cause of death. Verbal autopsies, reliable in this context, may still be missing cases where the victims, bitten in the night, die of, say, “early morning paralysis,” he had cautioned.

Findings that emerged from the PLoS NTD survey: Snakebite deaths occurred mostly in rural areas (97%), were more common in males (59%), and peaked at ages 15–29 years (25%) and during the monsoon months of June to September. Based on these facts, and the universally observed truth that snakes don’t go out of the way to attack humans, there are simple strategies to reduce risk of snakebites.

More effective cures

Community education should encourage victims to seek medical, rather than traditional, help as soon as possible and recommend safe and effective first aid methods, Warrell adds. Health workers, nurses and doctors should receive better training in the management of snakebites, especially in the use of anti-snake venom (ASV), which is the only specific antidote.

There is a great diversity of venomous snakes in India but the polyvalent ASV is only raised against the “big four”: the spectacled cobra, saw-scaled viper, Russell’s viper, and the common krait. And 80% of the venom used to generate ASV comes from snakes in and around Mahabalipuram, in Tamil Nadu, he says.

So in a new research project, herpetologists from the Madras Crocodile Bank, toxicologists and clinicians throughout the country will work together to test the effectiveness of this ASV against venoms of Russell’s vipers from other parts of the country. Evidence suggests that there is significant variation in venom composition and toxicity even for the same snake species across the country, says Romulus Whitaker, renowned conservationist, herpetologist, and founder-director of the Snake Park in Chennai.

Speaking from close to four decades of clinical experience in rural Maharashtra, Himmat Bawaskar, MD, of Bawaskar Hospital and Research Centre, Mahad, says that medical textbooks now devote pages to treating envenoming by scorpion and snakebites, which wasn’t the case when he graduated from medical school in 1976. Today, better transport to primary health centers has also helped in timely interventions. “Each PHC is provided enough anti-venom against scorpion and snake venom,” he says, but concedes that this neither of these facts may be true for the entire nation.

In 2001, in a communication with Lancet, Bawaskar had made the case for finding a chemical antidote for snakebite, similar to the inexpensive drug he has used to great effect in the treatment of scorpion bite. But funding for this alternative hasn’t been forthcoming so far.

The rigors of 21st century medicine have yet to be brought to bear fully on this ancient scourge.

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Prof. Rohini Godbole, particle physicist, is a researcher at the Indian Institute of Science, Bangalore. In a parallel universe, she would have been a Bank of Maharasthra employee: she was offered a job after she topped Pune University in B.Sc., Physics. “The salary was almost as much as my father’s at that time,” she recalls. A scholarly life, she decided, would suit her better. Today, she is part of a select group of scientists who will decide the design of the next-generation particle accelerator based on the outcome of experiments being run on CERN’s Large Hadron Collider (LHC).

Read more about her life and work here. pdf

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