̽��ֱ�� of Cambridge - ̽��ֱ�� of Washington

Cambridge partners with Schmidt Futures in new software engineering network

Anonymous — Wed, 19 Jan 2022 10:39:36 +0000

Schmidt Futures and its partner institutions are establishing the Virtual Institute of Scientific Software (VISS), starting with a network of four centres based at the ̽��ֱ�� of Cambridge, Georgia Institute of Technology, the Johns Hopkins ̽��ֱ�� and the ̽��ֱ�� of Washington.

This interdisciplinary virtual institute will address the growing demand for software engineers with backgrounds in science, complex data and mathematics who can build dynamic, scalable, open software to facilitate accelerated scientific discovery across fields.

While science has become increasingly reliant on complex programming and technology, many researchers lack the training or experience in software engineering, tools and methods to produce effective, reliable, and scalable solutions. As a result, successful research and scientific discovery is sometimes delayed as researchers looking to conduct further experiments struggle to adapt unstable and outdated programming.

VISS seeks to improve the quality of research, accelerate advancements and encourage scalable open-source solutions by providing scientific researchers with access to full-time professional engineers and state of the art technology to develop high quality, maintainable and adaptable software.

“Schmidt Futures’ Virtual Institute for Scientific Software will accelerate the pace of scientific discovery through the development of robust, well-engineered software, supporting longer-term platforms and systems, encouraging best practices in open science, and providing access to techniques such as high-end computing, massive databases, and machine learning,” said Elizabeth McNally, Executive Vice President, Schmidt Futures.

Cambridge's Institute of Computing for Climate Science (ICCS) will apply its existing expertise in climate sciences and artificial intelligence with the research teams from Schmidt Futures’ Virtual Earth Systems Research Institute (VESRI) to address the specific computation and research software needs in the area of climate modelling.

̽��ֱ��centre represents a collaboration between Cambridge Zero, the Departments of Computer Science and Technology, Applied Mathematics and Theoretical Physics, and ̽��ֱ�� Information Services. ̽��ֱ��other three centres will be dedicated to a range of scientific focus areas, including astrophysics, life sciences, engineering and climate.

“With this truly visionary new institute, Cambridge will blend its world-leading climate science, software engineering and computer science expertise,” said Vice-Chancellor Professor Stephen J Toope. “This interdisciplinary powerhouse will enable the development of next-generation climate models. We are delighted to be partnering with Schmidt Futures and engaging with the international research community to inform the response to our most urgent global challenge.”

̽��ֱ��ICCS will be led by Emily Shuckburgh (Academic Director; Cambridge Zero), Dominic Orchard (Co-director; Computer Science/Software Engineering), Chris Edsall (Co-director; Engineering), and Colm-cille Caulfield (Co-director; Science). All have a long-term research agenda to improve understanding of our changing climate through the development, implementation, maintenance, and dissemination of models for scientific computing, data assimilation and analysis.

Being part of the ̽��ֱ��, ICCS will also have a significant education and training component, through the commitment towards sharing its scientific insights openly and broadly. ICCS will play a key role in Cambridge Zero, the ̽��ֱ��'s climate change initiative, that is identifying routes to the creation of a sustainable, zero-carbon future for all.

Over the coming months, ICCS will build a team of researchers and software engineers who share the vision of the power of modern computer science, data science and software engineering for addressing the pressing challenges of our changing climate.

Director of Cambridge Zero and Academic Director of ICCS, Dr Emily Shuckburgh, said “ ̽��ֱ��Institute of Computing for Climate Science will be the first of its kind, supporting the application of the latest developments in computer science and data science to climate modelling. It is tremendously exciting to launch this Institute, which will be the core of an international network of climate research initiatives supported by Schmidt Futures, and will help drive forwards the frontiers of climate science.”

̽��ֱ��interdisciplinary network of centres, which will benefit from the experience of the Schmidt Software Academy at Caltech, will have an initial lifespan of five years.

Adapted from a release published by Schmidt Futures.

Software engineers will bridge the gap between modern science and scalable complex software at four leading universities.

̽��ֱ��Institute of Computing for Climate Science will be the first of its kind, supporting the application of the latest developments in computer science and data science to climate modelling

Emily Shuckburgh

Sir Cam

Centre for Mathematical Sciences

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Food and drinks industry uses non-profit organisation to campaign against public health policies, study finds

fpjl2 — Mon, 03 Jun 2019 08:07:13 +0000

̽��ֱ��study, published today in the journal Globalization and Health, analysed over 17,000 pages of emails obtained through Freedom of Information requests made between 2015 and 2018. ̽��ֱ��documents captured exchanges between academics at US universities and senior figures at a non-profit organisation called the International Life Science Institute, or ILSI.

Comprising of 18 bodies, each of which covers a specific topic or part of the globe, ILSI has always maintained its independence and scientific rigour, despite being funded by multinational corporations such as Nestle, General Mills, Mars Inc, Monsanto, and Coca-Cola.

Founded by former Coca-Cola senior vice president Alex Malaspina in 1978, ILSI states on its website that none of its bodies “conduct lobbying activities or make policy recommendations”. As a non-profit organisation, ILSI is currently exempt from taxation under US Internal Revenue codes.

However, researchers from the ̽��ֱ�� of Cambridge, London School of Hygiene and Tropical Medicine, ̽��ֱ�� of Bocconi, and US Right to Know, found emails explicitly discussing tactics for countering public health policies around sugar reduction, as “[T]his threat to our business is serious”.

These include exchanges with an epidemiology professor at the ̽��ֱ�� of Washington, as well as the US Centre for Disease Control’s then director of heart disease and stroke prevention, all strategising how best to approach the World Health Organisation’s then Director-General Dr Margaret Chan, to shift her position on sugar-sweetened products.

“It has been previously suggested that the International Life Sciences Institute is little more than a pseudo-scientific front group for some of the biggest multinational food and drink corporations globally,” said the study lead author Dr Sarah Steele, a researcher at Cambridge’s Department of Politics and International Studies.

“Our findings add to the evidence that this non-profit organisation has been used by its corporate backers for years to counter public health policies. We contend that the International Life Sciences Institute should be regarded as an industry group – a private body – and regulated as such, not as a body acting for the greater good.”

In one email, Malaspina, who also served as long-time president at ILSI, described new US guidelines bolstering child and adult education on limiting sugar intake as a “real disaster!”. He writes: “We have to consider how to become ready to mount a strong defence”. Suzanne Harris, then executive director of ILSI, was among the email’s recipients.

James Hill, then director of the Center for Human Nutrition at the ̽��ֱ�� of Colorado, was involved in a separate exchange on the issue of defending industry from the health consequences of its products. Hill argues for greater funding for ILSI from industry as part of “dealing aggressively with this issue”. He writes that, if companies keep their heads down, “our opponents will win and we will all lose”.

̽��ֱ��FOI emails also suggest ILSI constructs campaigns favourable to artificial sweeteners. Emails reveal Malaspina passing on praise from another former ILSI President to a former Coca-Cola employee and the Professor, describing both as “the architects to plan and execute the studies showing saccharine is not a carcinogen”, resulting in the reversal of many government bans.

̽��ֱ��FOI responses suggest that ILSI operates strategically with other industry-funded entities, including IFIC, a science communication non-profit organisation. “IFIC is a kind of sister entity to ILSI,” writes Malaspina. “ILSI generates the scientific facts and IFIC communicates them to the media and public.”

“ ̽��ֱ��emails suggest that both ILSI and IFIC act to counter unfavourable policies and positions, while promoting industry-favourable science under a disguised front, including to the media,” said Steele.

In fact, the emails suggest ILSI considers sanctioning its own regional subsidiaries when they fail to promote the agreed industry-favourable messaging. Correspondence reveals discussion of suspending ILSI’s Mexico branch from the parent organisation after soft drink taxation was debated at a conference it sponsored. Mexico has one of the highest adult obesity rates in the world.

Email conversations between Malaspina and the CDC’s Barbara Bowman are open about the need to get the WHO to “start working with ILSI again” and to take into account “lifestyle changes” as well as sugary foods when combatting obesity.

Further exchanges between Malaspina and Washington Professor Adam Drewnowski support ILSI’s role in this. Drewnowski writes of Dr Chan that “we ought to start with some issue where ILSI and WHO are in agreement” to help “get her to the table”.

In a further email, Malaspina points out that he had meetings with the two previous heads of the WHO, going back to the mid-90s, and that if they do not start a dialogue with Dr Chan “she will continue to blast us with significant negative consequences on a global basis”.

̽��ֱ��tide has begun to turn against ILSI in recent years. ̽��ֱ��WHO quietly ended their “special relations” with ILSI in 2017, and ILSI’s links to the European Food Safety Authority were the subject of enquiry at the European Parliament. ̽��ֱ��CDC’s Bowman retired in 2016, in the wake of revelations about her close ties with ILSI. Last year, long-time ILSI funder Mars Inc. stopped supporting the organisation. Much of the study’s correspondence precedes these events.

“It becomes clear from the emails and forwards that ILSI is seen as central to pushing pro-industry content to international organisations to support approaches that uncouple sugary foods and obesity,” added Steele.

“Our analysis of ILSI serves as a caution to those involved in global health governance to be wary of putatively independent research groups, and to practice due diligence before relying upon their funded studies.”

Reference
Are industry-funded charities promoting “advocacy-led studies” or “evidence-based science”?: a case study of the International Life Sciences Institute. Globalization and Health; 3 June 2019; DOI: 10.1186/s12992-019-0478-6

A new study shows how a non-profit research organisation has been deployed by its backers from major food and beverage corporations to push industry-favourable positions to policymakers and international bodies under the guise of neutral scientific endeavour.

We contend that the International Life Sciences Institute should be regarded as an industry group – a private body – and regulated as such, not as a body acting for the greater good

Sarah Steele

Photo by Peter Bond on Unsplash

High-angle photography of grocery display

Yes

Licence type:

Public Domain

Pilot programme encourages researchers to share the code behind their work

sc604 — Fri, 02 Jun 2017 07:30:00 +0000

A new pilot project, designed by a Cambridge researcher and supported by the Nature family of journals, will evaluate the value of sharing the code behind published research.

For years, scientists have discussed whether and how to share data from painstaking research and costly experiments. Some are further along in their efforts toward ‘open science’ than others: fields such as astronomy and oceanography, for example, involve such expensive and large-scale equipment and logistical challenges to data collection that collaboration among institutions has become the norm.

Recently, academic journals, including several Nature journals, are turning their attention to another aspect of the research process: computer programming code. Code is becoming increasingly important in research because scientists are often writing their own computer programs to interpret their data, rather than using commercial software packages. Some journals now include scientific data and code as part of the peer-review process.

Now, in a commentary published in the journal Nature Neuroscience, a group of researchers from the UK, Europe and the United States have argued that the sharing of code should be part of the peer-review process. In a separate editorial, the journal has announced a pilot project to ask future authors to make their code available for review.

Code is an important part of the research process, and often the only definitive account of how data were processed. “Methods are now so complex that they are difficult to describe concisely in the limited ‘methods’ section of a paper,” said Dr Stephen Eglen from Cambridge’s Department of Applied Mathematics and Theoretical Physics, and the paper’s lead author. “And having the code means that others have a better chance of replicating your work, and so should add confidence.”

Making the programs behind the research accessible allows other scientists to test the code and reproduce the computations in an experiment — in other words, to reproduce results and solidify findings. It’s the “how the sausage is made” part of research, said co-author Ben Marwick, from the ̽��ֱ�� of Washington. It also allows the code to be used by other researchers in new studies, making it easier for scientists to build on the work of their colleagues.

“What we’re missing is the convention of sharing code or the tools for turning data into useful discoveries or information,” said Marwick. “Researchers say it’s great to have the data available in a paper — increasingly raw data are available in supplementary files or specialised online repositories — but the code for performing the clever analyses in between the raw data and the published figures and tables are still inaccessible.”

Other Nature Research journals, such as Nature Methods and Nature Biotechnology, provide for code review as part of the article evaluation process. Since 2014, the company has encouraged writers to make their code available upon request.

̽��ֱ��Nature Neuroscience pilot focuses on three elements: whether the code supporting an author’s main claims is publicly accessible; whether the code functions without mistakes; and whether it produces the results cited. At the moment this is a pilot project to which authors can opt in. It may be that in future it becomes mandatory and only when the code has been reviewed will a paper then be accepted.

“This extra step in the peer review process is to encourage ‘replication’ of results, and therefore help reduce the ‘replication crisis’,” said Eglen. “It also means that readers can understand more fully what authors have done.”

An open science approach to sharing code is not without its critics, as well as scientists who raise legal and ethical questions about the repercussions. How do researchers get proper credit for the code they share? How should code be cited in the scholarly literature? How will it count toward tenure and promotion applications? How is sharing code compatible with patents and commercialization of software technology?

“We hope that when people do not share code it might be seen as ‘having something to hide,’ although people may regard the code as ‘theirs’ and their IP, rather than something to be shared,” said Eglen. “Nowadays, we believe the final paper is the ultimate representation of a piece of research, but actually the final paper is just an advert for the scholarship, which here is the computer code to solve a particular task. By sharing the code, we actually get the most useful part of the scholarship, rather than the paper, which is just the author’s ‘gloss’ on the work they have done.”

Adapted from a ̽��ֱ�� of Washington press release.

New project, partly designed by a ̽��ֱ�� of Cambridge researcher, aims to improve transparency in science by sharing ‘how the sausage is made’.

Having the code means that others have a better chance of replicating your work.

Stephen Eglen

Lorenzo Cafaro

Close up code

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

New details of TRAPPIST-1 system’s outermost planet confirm earlier predictions

sc604 — Mon, 22 May 2017 15:00:00 +0000

̽��ֱ��observations confirm, as had been predicted, that the seventh and outermost planet, TRAPPIST-1h, orbits its star every 18.77 days. ̽��ֱ��results are reported in the journal Nature Astronomy.

“TRAPPIST-1h was exactly where our team predicted it to be,” said Rodrigo Luger, a PhD student at the ̽��ֱ�� of Washington and the paper’s lead author. ̽��ֱ��researchers discovered a mathematical pattern in the orbital periods of the inner six planets, which was strongly suggestive of an 18.77 day period for planet h.

TRAPPIST-1A is a middle-aged, ultra-cool dwarf star, much less luminous than the Sun and only a bit larger than Jupiter. ̽��ֱ��star, which is nearly 40 light years away in the constellation of Aquarius, is named after the ground-based Transiting Planets and Planetesimals Small Telescope (TRAPPIST), the facility that first found evidence of planets around it in 2015.

̽��ֱ��TRAPPIST survey is led by Michaël Gillon of the ̽��ֱ�� of Liège, Belgium, who is also a co-author on this research. In 2016, Gillon’s team announced the detection of three planets orbiting TRAPPIST-1 and this number was upped to seven in a paper published earlier this year. All seven planets are deemed temperate, meaning that under certain geologic and atmospheric conditions, water could exist in a liquid form. Three of the planets are particularly optimal. In addition the TRAPPIST-1 system is currently the most convenient to remotely explore the atmospheres of planets with sizes similar to Earth.

Such exoplanets are detected when they transit, or pass in front of, their host star, blocking a measurable portion of the light. “We only captured one transit of TRAPPIST-1h last autumn. However, the resonant pattern formed by the other six planets, and the time TRAPPIST-1h takes to pass in front of its star, allowed the team to deduce its orbital period with a precision of a few minutes,” said co-author Amaury Triaud, a Kavli Exoplanet fellow Amaury Triaud at Cambridge’s Institute of Astronomy. “This is absolutely remarkable! TRAPPIST-1h represents a perfect illustration of the power of the scientific method, of its ability to make predictions that can later be verified.”

̽��ֱ��inner six planets occupy orbits consistent with being in ‘resonance’. All orbital periods are mathematically related and slightly influence each other. Orbital resonances can also be found in our solar system. For instance, Jupiter’s moons Io, Europa and Ganymede are set in a 1:2:4 resonance, meaning that while Ganymede orbits Jupiter once, Europa does so twice, and Io four times. ̽��ֱ��prediction of TRAPPIST-1h’s orbital period principally relied on extrapolating the known resonant configuration of the inner six planets, to the seventh. This prediction was later confirmed.

̽��ֱ��team analysed 79 days of observation data from K2, the second mission of the Kepler Space Telescope, and was able to recover four transits of TRAPPIST-1h across its star. ̽��ֱ��K2 data was also used to further characterize the orbits of the other six planets, help rule out the presence of additional transiting planets, and learn the rotation period and activity level of the star.

TRAPPIST-1's seven-planet chain of resonances establishes a record among known planetary systems. ̽��ֱ��resonances strengthen the long-term stability of the planetary system. It is also likely that these orbital connections were forged early in the life of the TRAPPIST-1 system, when the planets and their orbits were not fully formed.

“Observing TRAPPIST-1 with K2 was an ambitious task,” said Marko Sestovic, a PhD student at the ̽��ֱ�� of Bern and second author of the study. In addition to the complicated signals introduced by the spacecraft’s wobble, the faintness of the star in the optical (the range of wavelengths where K2 observes) placed TRAPPIST-1h “near the limit of what we could detect with K2,” he said. To make matters worse, Sestovic said, one transit of the planet coincided with a transit of TRAPPIST-1b, and one happened during a stellar flare, adding to the difficulty of the observation. “Finding the planet was really encouraging,” Luger said, “since it showed we can still do high-quality science with Kepler despite significant instrumental challenges.”

̽��ֱ��research was funded by the NASA Astrobiology Institute via the UW-based Virtual Planetary Laboratory as well as a National Science Foundation Graduate Student Research Fellowship, the Swiss National Science Foundation, the European Research Council and the UK Science and Technology Facilities Council, among other agencies. This work was partially supported by a grant from the Simons Foundation.

Based on a press release by the ̽��ֱ�� of Washington.

Reference:
Rodrigo Luger et al. 'A seven-planet resonant chain in TRAPPIST-1.' Nature Astronomy (2017). DOI: 10.1038/s41550-017-0129

An international team of astronomers, including researchers from the ̽��ֱ�� of Cambridge, used data gathered by the Kepler Space Telescope to observe and confirm details of the outermost of seven exoplanets orbiting the star TRAPPIST-1.

TRAPPIST-1h represents a perfect illustration of the power of the scientific method, of its ability to make predictions that can later be verified.

Amaury Triaud

IoA/Amanda Smith

Artist's impression of TRAPPIST-1

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

A whole host of options

cjb250 — Fri, 09 Oct 2015 08:30:04 +0000

Professor Lalita Ramakrishnan is, it’s fair to say, a world authority on the biology of TB. She studies the disease – one which most people will know of as a disease of the lungs – using what at first sight seems an unusual model: the zebrafish.

“What most people don’t realise is that about 40% of human TB occurs outside the lungs,” explains Ramakrishnan. “It can infect the brain, bone, heart, reproductive organs, skin, even the ear. In fact, TB infection is a basic biology question, and this is the same in zebrafish as it is in humans.”

TB is caused by Mycobacterium tuberculosis, which is generally transmitted from person to person through the air. It has been around since at least the Neolithic period, but its prevalence in 19th-century literature led it to be considered something of a ‘romantic’ disease. ̽��ֱ��truth is a long way from this portrayal. ̽��ֱ��disease can cause breathlessness, wasting and eventual death. And while treatments do exist, the drug regimen is one of the longest for any curable disease: a patient will typically need to take medication for six months.

Ramakrishnan is involved in a new trial due to start soon that might allow doctors to reduce the length of this treatment. She is cautiously optimistic that it can be reduced to four months; if successful, however, it may eventually lead to treatments more on a par with standard antibiotic treatments of a couple of weeks.

̽��ֱ��trial builds on work in zebrafish carried out by Ramakrishnan and colleagues at the ̽��ֱ�� of Washington, Seattle, before she moved to the Department of Medicine in Cambridge in September 2014. These small fish, which grow to the length of a little finger, helped her and collaborator Professor Paul Edelstein from the ̽��ֱ�� of Pennsylvania (currently on sabbatical in Cambridge) to make an important discovery that could explain why it takes a six-month course of antibiotics to rid the body of the disease (rather than seven to ten days that most infections take) and yet in the lab can easily be killed.

Within our bodies, we have a host of specialist immune cells that fight infection. One of these is the macrophage (Greek for ‘big eater’). This cell engulfs the TB bacterium and tries to break it down. This, together with powerful antibiotics, should make eliminating TB from the body a cinch. Ramakrishnan’s breakthrough was to show why this wasn’t the case: once inside the macrophages, TB switches on pumps, known as ‘efflux pumps’. Anything that we throw at it, it just pumps back out again.

“Once we’d identified the pumps, we started to look for drugs that are out there in the market and tested a few of them,” she explains. “We found that verapamil, an old drug, made the bacteria susceptible to two of the antibiotics we use to fight TB.”

̽��ֱ��trial of verapamil, which is commonly used to treat high blood pressure, is due to start soon at the National Institute for Research in Tuberculosis (NIRT) in Chennai, India.

Ramakrishnan is one of a number of brilliant minds working as part of a collaboration between the NIRT and the ̽��ֱ�� of Cambridge to apply the very latest in scientific thinking and technology to the problem of TB.

An expansion of this collaboration has now become possible through the recent award of a £2 million joint grant from the UK Medical Research Council (MRC) and the Department of Biotechnology (DBT) in India, which will enable the exchange of British and Indian researchers. For Professor Sharon Peacock, the UK lead on the proposal, this means an opportunity to train a new cohort of early-career researchers in an environment where they will have access to outstanding scientific facilities and training, at the same time as becoming familiar with the clinical face and consequences of TB for people in India.

“India is home to a large pool of talented young people with the potential to help fight back against this deadly disease,” says Peacock. “Developing a close collaboration between Cambridge and Chennai involving two-way traffic of scientists and ideas is an exciting opportunity to start to tap into this.”

There are few places more suitable for the proposed work than India. According to the World Health Organization, India is home to almost one in four of all worldwide cases of TB, with over two million newly diagnosed cases in 2014.

Not only that, but it is one of the countries that has seen an increase in the number of cases of drug resistance to TB – including ‘multi-drug’-resistant, and even more worrying, ‘extremely’ drug-resistant strains of TB against which none of our first- and second-line drug treatments work. In part, this increase reflects improved access to diagnostic services, but the situation highlights why new approaches to tackling the disease are urgently needed, says Professor Soumya Swaminathan, Director of NIRT and the India lead in the collaboration.

“So far, the treatment of TB has focused almost exclusively on using drugs to try to kill the bacteria directly, but there’s increasing evidence that there may be benefits to targeting the host. TB is very clever and it manipulates the host immune system to its own advantage, so if we could use drugs to help the immune system, then we may be able to make it more effective.”

This is the approach that Professors Ken Smith and Andres Floto from the Department of Medicine at Cambridge, also part of the collaboration, are taking. Smith is looking at the role that specialist immune cells known as T cells play in the persistence of multi-drug-resistant strains of TB. His group has evidence that around two thirds of the population have T cells which have a tendency to become ‘exhausted’ when activated.

“It might be that exhausted T cells can’t fight multi-drug-resistant TB effectively, in which case we need to find a way to overcome this exhaustion and spur the T cells on to rid the body of the disease,” says Smith.

For Floto, the key may lie in the role played by the macrophages and their otherwise voracious appetites. As their Greek name suggests, macrophages ‘eat’ unwanted material (surprisingly similar in action to Pac-Man), effectively chewing it up, breaking it down and spitting it out again.

This process, known as autophagy (‘self-eating’), is a repair mechanism for clearing damaged bits of cells and recycling them for future use, but also works as a defence mechanism against some invading bacteria. So why, when it engulfs TB, does the bacterium manage to avoid being digested?

“Autophagy is partially inhibited by TB itself, but we found that if you overstimulate this mechanism – like flooring the accelerator of a car – you can overcome the bacteria,” explains Floto. “Clearly this will be applicable to normal TB, but we already have drugs that are effective against this. We want to know if this would work against multi-drug-resistant strains.”

Floto and colleagues already have a list of potential drugs that can stimulate autophagy, drugs that have already been licensed and are in use to treat other conditions, such as carbamazepine, which is used to treat epileptic seizures. These drugs are safe to use: the question is, will they work against TB?

“We’ve already shown that carbamazepine stimulates autophagy in cells to kill TB – even multi-drug-resistant TB. We now want to refine it and test it in mice and in fish, alongside a shortlist of around 30 other potential drugs,” he adds.

TB evolves through ‘polymorphisms’ – spontaneous changes in the letters of its DNA to create variants. Because the drug regimen to fight the disease lasts so long, many patients do not take the full course of their medicines. If the TB is allowed to relapse, it can evolve drug resistance.

These patterns of resistance can be detected using genome sequencing – reading the DNA of the bacteria. Peacock believes this technique may be able to help doctors more easily diagnose drug resistance in patients.

“TB is very slow to grow in the laboratory, which means that testing an organism to confirm which antibiotics it is susceptible or resistant to can take several weeks, especially in the case of more resistant strains,” she says. “There is increasing evidence that antibiotic resistance can be predicted from the genome sequence of the organism, and we want to establish and evaluate this technology in India, where it is needed.”

This sequencing data could also then help inform the search for new drugs, explains Professor Sir Tom Blundell from the Department of Biochemistry. He is no stranger to TB: his grandfather died from the disease shortly after the war – though, as Blundell points out, this strain of TB is far less common now, as the organism has evolved in different communities throughout the world.

“We can take the polymorphisms and ask questions such as ‘What does this mean for the use of current drugs?’” says Blundell. “ ̽��ֱ��nature of the polymorphisms in the TB genome sequence of an infected individual can give us information on where that person was infected and what are the drugs that might be most effective. We can then begin to look at new targets for particular polymorphisms.”

Blundell plans to take the information gathered through the Chennai partnership and feed it into his drug discovery work. He takes a structural approach to solving the problem: look at the shape of the polymorphism and its protein products and try to find small molecules that can attach to and manipulate them. In essence, it’s akin to picking a lock by analysing the shape of its mechanism and trying to identify a key that could turn it, thus opening the door.

Yet even if the Chennai venture is successful, and research from the partnership leads to a revolution in how we understand and treat TB, the team recognise that this is unlikely to be enough to eradicate the disease for good.

“TB is as much a public health issue as one of infectious diseases,” says Ramakrishnan, pointing to Europe, where even before the introduction of antibiotics, the disease was already on the decline. “We need better nutrition, better air, less smoking, reductions in diabetes.”

Swaminathan agrees. “TB is very much associated with poverty and all the risk factors that go with it,” she says. “When people are living in very crowded conditions, when they’re malnourished, TB is going to continue to spread. This is happening in the slums of Mumbai, for example, where we’re seeing a mini-epidemic of multi-drug-resistant TB. Unless we see a rapid improvement in the living standards of people we’re not going to see a very major effect. There’s only so much we can do biomedically.”

Inset image: Macrophage engulfing Tuberculosis pathogen (ZEISS Microscopy).

Almost one in four of the world’s cases of tuberculosis (TB) are in India and the disease is constantly adapting itself to outwit our medicines. Could the answer lie in targeting not the bacteria but its host, the patient?

What most people don’t realise is that about 40% of human TB occurs outside the lungs ... It can infect the brain, bone, heart, reproductive organs, skin, even the ear

Lalita Ramakrishnan

Calcutta Rescue

Picture to educate people in villages that have no medical service about the spread of TB

̽��ֱ��Next Generation

If there’s one thing on the side of science v. TB, it’s the wealth of talent available in India.

Professor Sir Tom Blundell is quick to praise the Indian postdocs that come to work in his lab. “They tend to be naturally very inquisitive and interactive, with very enquiring minds,” he says.

This is something with which Professor Ashok Venkitaraman, Director of the Medical Research Council (MRC) Cancer Unit at Cambridge, wholeheartedly agrees. He has helped establish the Center for Chemical Biology and Therapeutics (CCBT) in Bangalore in part, he says, because “the number of really bright, well-trained young scientists in India is huge. ̽��ֱ��level of enthusiasm and commitment is something I find quite exceptional.”

̽��ֱ��CCBT is an inter-institutional centre that links the Institute for Stem Cell Biology and Regenerative Medicine and the National Center for Biological Sciences, both of which are world-class Indian research institutes studying fundamental biology. However, argues Venkitaraman, India needs the capacity to translate fundamental research to clinical application.

It is to help bridge this gap that the CCBT was established, with funding from the Department of Biotechnology (DBT) in India, recently supplemented by a £2 million joint award from the UK MRC and the DBT. ̽��ֱ��idea is to find innovative ways to discover ‘next-generation’ medicines against human diseases, by coupling biological research that reveals novel drug targets with approaches in chemistry and structural biology that create potential drug candidates.

Although Venkitaraman’s interest is in cancer, he predicts the work of the CCBT will be “disease agnostic”, because similar types of novel drug targets have been implicated in infectious diseases, cancer and even developmental defects.

“We desperately need to develop new medicines not just for currently problematic diseases like cancer and TB, but also for the new challenges that are being thrown at us all the time – antibiotic resistance, new infections, metabolic syndromes and diseases of ageing, for example. Nowhere is this need more critical than in emerging nations like India where the spectrum of disease is distinct from countries like the UK.”

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution-Noncommercial-ShareAlike