Monthly Archives: August 2017

IUCr 2017 Hyderabad:Blog Day 8, Monday 28 August: Crystallography in Space

Day 8, Monday 28 August: Crystallography in Space

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK

In general terms, crystallography can be thought of as a science of the very small, and space science as a science of the very large. For most crystallographers, therefore, it might take a bit of imagination to link the two. But crystallography does have a role in space science, and this was explored in a popular and thought-provoking special session in Hyderabad.  This came about as a result of a collaboration between IUCr and the Committee on Space Research (COSPAR) that was set up during the International Year of Crystallography; COSPAR and IUCr organised a capacity-building workshop on crystallography in space research in Puebla, Mexico in April 2016, and the IUCr session was organised as a follow-up to that. Its chair, Hanna Dabkowska (Vice President, IUCr 2017-2020) from McMaster University in Canada, had been one of the lecturers in Puebla.

The first talk, by NASA’s Dave Blake, had one of the most immediately engaging titles of any conference presentation: ‘Mineralogical Results from the Mars Science Laboratory Rover Curiosity’. The results he presented came from the first in situ analysis of minerals on the surface of Mars. The rover vehicle Curiosity is the largest exploration vehicle to have yet been landed on the surface of the ‘red planet’. It collects small specimens of rock and dust from the Martian surface to analyse using its 10 complex instruments; the initial aim of all these experiments was to answer the question ‘has it ever been possible for Mars to support life?’ As the Martian environment bears some similarities to those that probably existed on Earth when life first emerged there 3.7 billion years ago, a positive answer to this question would have important implications for theories of the origin of life. It landed in a crater named Gale in August 2012 and will remain on Mars for about two more years.

Blake explained that the ‘Swiss army knife’ of experiments carried by Curiosity includes a diffractometer about the size of a large briefcase. This instrument, which has been named CheMin, is being used to analyse bedrock from Gale and materials taken from the sides of Mount Sharp, a 3-mile high mountain (more accurately, mound of rubble) in the centre of the crater. Briefly, X-ray diffraction patterns from these minerals were consistent with the theory that the rover had landed at the end of an ancient river system and that the environment had gradually dried out and oxidised over geological time. If this is correct, Curiosity’s mission has already succeeded: Gale Crater is ‘an environment that could once have supported some form of life’. If you like, you can explore the data for yourself; it is all free to download.

The next two speakers, Tomoki Nakamura from Tohoku University, Japan and Helen Maynard-Casely from the Australian synchroton site, ANSTO, took crystallography even further afield by presenting, respectively, studies of minerals from small asteroids and from Saturn’s moon Titan. The small asteroids were the first planet-like bodies to be formed in the Solar System; Nakamura uses both X-ray crystallography and basic mineralogy to analyse samples of dust and debris that have been returned to Earth from one of these, the oddly shaped near-Earth asteroid Itokawa, by the Hayabusa spacecraft. His group has been able to piece together a ‘life history’ for this asteroid from the point when it was formed over 4 billion years ago. This involves intense internal heating and cooling followed by an impact with another space body that shattered it into many fragments; many of these fragments then re-accreted to form the smaller, peanut-shaped object we see today. This project is part of the Japanese-led ISAS Small Body Exploration Strategy to analyse the structures of small asteroids and meteorites, which is expected to last well into the 2020s.

Maynard-Casely began her engaging talk by reminding us of Blake’s comment that CheMin, on the Curiosity Rover, was the only diffractometer located outside the Solar System and of Nakamura’s comments about the complexity of returning samples to Earth from Itokawa, which is far closer to Earth than Saturn. Studying the materials on Titan’s freezing surface, where the temperature is always close to 90K, is therefore very difficult. This surface consists of ‘lakes and seas’ and areas that are covered by crystalline residues analogous to those seen on dried-up lake beds. But the environment is far too cold for water: remote analysis of samples obtained by a small ‘lander’ jettisoned from the Cassini space probe identified high concentrations of benzene and ethane, and a benzene crystal form with a shorter bond length than normal benzene crystals.  Maynard-Casely mixed the two compounds in her lab in conditions that mimic those on Titan, and formed a novel material: a co-crystal with ethane molecules inhabiting the channels between the benzene rings. She is beginning to produce a ‘mineralogy’ of organic materials thought to exist on icy moons like Titan.

The formal session ended with presentations by Yuki Kimura from Hokkaido University, Sapporo, Japan, on the formation of dust particles under micro-gravity and by Giuditta Perversi, a Ph.D. student at Edinburgh University, Scotland, on the low-temperature properties of magnetite. They were followed by a lively discussion; it is clear that the collaboration between COSPAR and IUCr has many years to run.


IUCr 2017 Hyderabad:Blog Day 7, Sunday 27 August: Building BRICS to collaboration in crystallography

Day 7, Sunday 27 August: Building BRICS to collaboration in crystallography

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK

One of the most interesting series of sessions at IUCr has taken the overall theme of ‘crystallography in emerging nations’. Out of these, the one held on Saturday afternoon – ‘the role for development in the BRICS countries’ – will be of most interest to crystallographers in the host nation, India. The acronym BRICS stands for five large middle income countries: Brazil, Russia, India, China and South Africa. These disparate countries nevertheless share some important characteristics. They are economically important with large populations (India and China are the two most populous countries on earth) and on average fast-growing economies. Together, they account for about 40% of the world’s population. All have established communities of scientists working in many disciplines, including crystallography; this short session explored how they could work together more.

The session began with a short introduction by two South Africans, Jean-Paul Ngome Abiaga, who is now based in France working in UNESCO’s Capacity Building in Science and Engineering section, and Andreas Roodt from the University of the Free State. They described current initiatives for promoting cooperation between the five countries, including the BRICS Scientific, Technological and Innovation Framework Programme for funding multinational research and innovation projects. Modelled on the European Union’s Framework programmes if on a much smaller scale, this supports projects in 10 thematic areas; the two that are of most interest to crystallographers are ‘materials science, including nanotechnology’ and ‘biotechnology and medicine’. Applications should include partners from at least three BRICS countries. This is a promising scheme, but one with undoubted bureaucratic ‘teething problems’: its first call for proposals closed in August 2016, but the first grants are only now being awarded.

One senior scientist from each country then took to the floor to present some aspect crystallography there. The Russian representative (a late replacement for Mikhail Kovalchuk) described her country’s long history in the subject, which goes back to Evgraf Fedorov’s derivation of the 230 space groups in 1891. Distinguished crystallographers of the Soviet era include Alexey Shubnikov, who was one of the founders of the IUCr. Since the 1990s, Russian science, like much of Russian society, has turned west towards Europe and Russia is a key participant in (for example) the European XFEL project. Separately, Alexander Blagov from the Russian Academy of Science in Moscow described research at one of Russia’s own ‘mega-facilities’, the Kurchatov Synchrotron Radiation Source.

Marcia Fantini from the University of Sao Paolo in Brazil focused on opportunities for crystallographers in her country today. The only synchrotron light source in Latin America is based there, a second is under construction and there are 17 research groups in the country with crystallography as their principal focus. The Chinese perspective was presented by Xiao-Dong Su from Peking University, Beijing, who remembered hosting the then frail, 83-year-old Dorothy Hodgkin among many hundreds of delegates at the 16th IUCr congress there in 1993.  Chinese crystallography has developed rapidly since then, following the rapid growth of the Chinese economy, and many structural scientists are returning from positions in the US, Europe and Japan. There are plans to update at least one of the three Chinese synchrotrons, and to build a free electron laser facility. South Africa is the only BRICS country not to have its own synchrotron, and, indeed, there are none in Africa. However, as Susan Bourne of the University of Cape Town said, its crystallography community is ‘small but very active’. And it, too, has a long history, going back to Reginald James, a professor at the same institution who had studied under W.L. Bragg in Manchester, UK. His students in South Africa included Aaron Klug, who was to win the 1982 Nobel prize for chemistry for structures of protein-nucleic acid complexes. It must be admitted that James is best known internationally as a member of Ernest Shackleton’s ill-fated expedition to the South Pole.

The Indian slot, taken by A. Nangla from CSIR in Pune, took a rather different form. Rather than presenting crystallography in India, he described a problem that he thought scientific collaboration between BRICS countries might contribute to solving: the often-quoted gap between basic research and application in the ‘real world’. This gap is bridged faster when there is a recognised need for the technology (‘market pull’ rather than ‘technology push’). He suggested that it might be particularly useful for BRICS crystallographers to collaborate in some specific areas with known applications and where they have established research strength, and cited MOFs as an example. These have many current and potential applications, including gas storage, photocatalysis and drug delivery.

These talks were followed by two shorter ones by younger scientists from India and Russia, describing research in crystal growth and hydrogen bonding respectively, and a ‘perspective on the BRICS initiative’ presented by three South African PhD students. The meeting ended with a round table discussion with a panel that included John Helliwell from the University of Manchester, UK, as well as the speakers. Almost all contributions were very positive about the potential for collaboration between the countries although there was some disagreement about the form that any grant programme should take, and there was much support for delegates from other African countries where crystallography is less advanced. If the BRICS initiative is handled well, there are clearly many opportunities for it to support crystallography and other structural sciences throughout the developing world.


IUCr 2017 Hyderabad:Blog Day 6, Saturday 26 August: Imaging Protein Dynamics

Day 6, Saturday 26 August:Imaging Protein Dynamics

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK

One of the most exciting developments in macromolecular crystallography in the last decade – and one that is already proving game-changing for the discipline – is the use of exceptionally fast and intense pulses of X-rays generated by free-electron lasers to image proteins in motion. Free-electron laser facilities are more complex and expensive to build even than synchrotrons, and only a handful have come on line so far. John Spence of the Physics department at Arizona State University, who gave the second plenary lecture at IUCr 2017, is the director of one of these: the NSF-funded BioXFEL, which is physically located in Buffalo, New York.

Spence studied for his Ph.D. in Melbourne, Australia and spent a few years as a postdoc in the University of Oxford, UK before moving to Arizona in 1976. During over four decades there he has accumulated honours, including foreign membership of the Australian Academy of Science and the UK’s Royal Society.  He spent many productive years working in protein electron microscopy before switching, fairly late in his career, to the emerging field of free electron laser crystallography.

He began his talk by quoting the great US physicist, Richard Feynman, as saying that “every living thing can be understood by the wiggling and jiggling of atoms”. He remembered having been told as a student in the early 1970s that it would never be possible to visualise atoms in motion; now, thanks to free-electron lasers (which were invented in 1971, but not used in crystallography for over thirty years) this has become a cornerstone of his research. He paid a generous tribute to Henry Chapman, who leads the free electron laser facility at DESY in Hamburg, Germany, whose “drive, ambition and deep understanding of diffraction physics” have played an important part in establishing the technique in structural biology.

Free-electron lasers work by wiggling fast-moving electrons sideways as they pass through a magnetic field. This generates tiny pulses of X-ray photons that last no more than a few femtoseconds (1fs = 10-15s) and that can be used instead of lower-intensity X-ray beams in protein crystallography. This offers numerous advantages: the pulses are so fast that they cause little damage to protein crystals, despite their intensity; they can take consecutive ‘snapshots’ of proteins moving at room temperature in near real time; and they can generate structures successfully from crystals that are too small for conventional X-ray crystallography.

Spence spent much of the rest of his talk describing examples of protein structures that have been studied using this approach and where new insights have been generated. It is now possible to take ‘snapshots’ of proteins in motion only about 150 fs apart, which is fast enough to resolve the process of photon absorption by retinal bound to rhodopsin in the human eye.  It is therefore possible to observe the stages in the cis-trans isomerisation from 11-cis-retinal to the all-trans isomer, which leads to a conformational change in rhodopsin that activates its bound G-protein.

Light sensitive reactions are some of the easiest to observe using this technique, but only a small fraction of proteins are in fact light sensitive. Spence described how it can also be used to look at reactions that are triggered by mixing, such as enzyme catalysis. Here the components to be mixed are placed in capillary tubes one inside each other; the protein is micro-crystalline and the reaction is triggered once the components are combined and the ligand has diffused into the micro-crystals. He explained how his group produces prototypes of the nanoscale components necessary for this technology using a 3D printer before describing two examples – visualisations of the mechanisms of gene expression regulation with riboswitches, and beta-lactamase binding to penicillin antibiotics – in some detail. The beta-lactamase example is particularly important because this enzyme is one of the commonest causes of antimicrobial resistance.

In the final part of his talk, Spence discussed some recent developments and other novel ideas that are still on the drawing board. It is now possible to study the structures of membrane proteins with laser-generated X-ray beams by delivering nanocrystals of the proteins using a tube of viscous material, memorably described as both a ‘grease gun’ and a ‘toothpaste jet’.  This – and the visualisation of intact virus particles – is still tricky and time-consuming; in contrast, nanocrystals of soluble proteins are becoming tractable enough that it is possible to ‘shoot first, ask questions afterwards’. The minimum X-ray pulse size is becoming even shorter, with a few machines generating pulses only a few tens of attoseconds (1as = 10-18s) long. He described briefly some of the experiments that will become possible once this type of laser is in routine use for crystallography. And, having started with a quote from Feynmann, he ended with one from a scientist who flourished some 150 years earlier. As Sir Humphrey Davy, the inventor of electrochemistry, wrote in 1806 (in paraphrase): “Nothing promotes the advancement of science so much as a new instrument”.

IUCr 2017 Hyderabad:Blog Day 5, Friday 25 August: Metal-Organic Frameworks as Porous Dynamic Structures

Day 5, Friday 25 August: Metal-Organic Frameworks as Porous Dynamic Structures

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK

Every IUCr congress includes three plenary lectures by distinguished scientists from different areas of crystallography. The first plenary of the 2017 meeting was given by Professor Susumu Kitagawa, the director of the Institute for Integral Cell-Material Sciences (iCeMS) in Kyoto, Japan. He was introduced by the current IUCr President, Professor Marvin Hackert of the University of Texas at Austin, Texas, USA.

Hackert began with a potted history of Kitagawa’s research career, which started in the 1970s with a PhD in hydrocarbon chemistry at the University of Tokyo. Apart from a year at Texas A & M University he has spent his entire career in Japan, moving first to the private Kindai University in Osaka and then Tokyo Metropolitan University. He was appointed as a professor in the chemistry department of Kyoto University in 1998 and has remained there ever since. His time in Kyoto, in particular, has been marked by a succession of prestigious awards including, earlier this year, the 58th Fujihara Award. This yearly award is given by the Fujihara Foundation of Science to “researchers who have made significant contributions to scientific and technological advancement”.

Kitagawa began by dedicating his lecture to a great French materials scientist, Gérard Férey, who had made significant contributions to the crystal chemistry of porous solids and had sadly died a few days before the start of the meeting at the age of 76. He introduced the main part of the lecture by referring to the pressing need for novel materials in order to maintain the world’s rapidly growing population while remaining within ecological limits. Gases have an important role to play here, as energy sources and in manufacturing, but they also have disadvantages: they are very difficult to control and particularly to store. Porous materials can hold and store gases, and transport; Kitagawa has spent much of his career studying novel materials known generally as porous coordination polymers (PCPs) and a sub-class of these, metal-organic frameworks or MOFs.

In very general terms, these materials can be thought of as regular building frameworks on the nanoscale, with tiny, regularly-spaced ‘holes’ that can hold gas molecules. They typically form crystalline particles with each ‘side’ about 1mm in length with the repeat unit – the ‘block’ from which the particle is built up – about 1nm3. Strictly speaking a porous coordination polymer is defined as a compound with repeats that extend in one, two or most often three dimensions, and MOFs are PCPs with metals incorporated into the framework.

Since the first MOFs were synthesised, three ‘generations’ of these materials have been defined. The structures of first-generation MOFs were very fragile and they could collapse after the gas they were holding was removed. Second- and third-generation MOFs retain their structure when gas is removed and are said to have permanent porosity. Their ‘very special’ properties combine some that are typical organic solids (like softness) with others that are more typical of metals (like crystallinity).

These soft porous compounds have many uses, including the storage and transport of dangerous gases. Kitagawa illustrated this point with a photo of an object that ‘[had been] a van’ that was transporting acetylene (C2H2) when the gas exploded; this could have been avoided if the acetylene had been stored in the pores of a MOF. Chemical separation processes such as distillation use an extraordinarily high proportion of the world’s energy resources, and these versatile compounds offer opportunities to make several of these more energy-efficient and thus ‘change the world’ .

Kitagawa ended his lecture with a rather complex exploration of some properties that can be altered by changing the nature of the metal and organic parts of a MOF. The novel ‘fourth-generation’ MOFs that are currently being designed have even more complex and varied properties that are affected by, for example, the material’s anisotropy, the number and nature of any defects and the pore size. And although they are generally crystalline solids at room temperature, they change phase to form liquids or glasses when temperature and pressure are raised; these, too, have interesting properties, and some powdery crystals re-form as spherulites when melted and then cooled. There are bound to be MOFs yet to be discovered that will have even more unusual and useful properties. In thanking Kitagawa for an excellent lecture that had held the attention of the large audience throughout, Hackert pointed out that there is still much to discover in this exciting field for today’s young scientists.


IUCr2017 Hyderabad: Blog Day 4, Thursday 24 August: Dragons’ Den

Day 4, Thursday 24 August: Dragons’ Den

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK

The TV show Dragons’ Den was invented in Japan but has become a worldwide brand. For anyone who has managed to avoid it so far – any residents of Mars, for example – it involves entrepreneurs pitching their business ideas to an audience of investors, or ‘dragons’, who quiz them in depth before deciding whether and how much to invest in the embryo businesses. Many variants of the Den have been spawned: the last to date, but by no means the least, in crystallography.

Regular #IUCr2017 delegates who are under the age of 35 and have no permanent academic position were encouraged to submit a proposal for research funding before the date of the congress, and the best of these have been chosen for presentation to a panel of senior scientists or ‘dragons’. The dragons’ task is then to choose the best ideas to receive INR 1,50,000 in grant funding. The idea proved very popular with younger delegates, and a large number of good proposals were received. No fewer than 43 were chosen to pitch their ideas in two sessions, 22 this afternoon (Thursday 24th) and the remaining 23 on Saturday morning.

The rules of the game were simple. Each finalist had two minutes to present his or her idea, interrupted by a large placard after 90 seconds and a final bell after which the presentation had to stop. The dragons – Ashwini Nangia, Massimo Nespolo, Amit Sharma, Christian Lehmann and Keith Moffatt – then had four minutes to grill the candidate.

Twenty-one candidates entered the Den on Thursday, as one was unable to attend at the last minute. The slick, fast-moving format and the eclectic nature of the students’ interesting ideas ensured that the session held the audience’s attention throughout. One or more presenters cited almost every technique that main meeting covers, except for exceptionally expensive ones: not surprisingly, neither high resolution electron microscopy nor free electron laser spectroscopy got a mention.

There were far too many presentations to describe here. Those that caught this blogger’s attention included a proposal to kick-start protein crystallography in Tunisia through collaborating with ESRF in Grenoble; a study of the mechanism of aldose-aldose oxidoreductases; and an exploration of the idea that a few bacterial species can incorporate arsenic into their DNA backbones in place of phosphorus.

The audience had not been told anything of what the dragons might have been looking for, but the questions that cropped up again and again gave some of it away. Many were quizzed about the references in their proposals; they had clearly been asked to cite at least two relevant research papers and to avoid self-citation. Many were asked exactly what they would spend the award money on if they won, which showed up ideas that were too ambitious or too vague. Some projects, however, fit the sum offered just right; the audience clearly warmed to Atahar Parveen, a postdoc in Hyderabad, who wanted to buy a computer so she could run simulations from home and spend more time with her young daughters. A few competitors were also caught out by being asked scientific questions linked to their proposals that they had not quite been expecting.

After the last candidate had made his pitch, the dragons retreated into another room to deliberate. This did not take long, and representatives of the event sponsors, STOE and Elsevier, then announced the two worthy winners. STOE, based in Darmstadt, Germany, has been manufacturing equipment for the ‘non-destructive’ analysis of crystals and powders since before X-rays were discovered, and now makes diffractometers; the global publishing giant Elsevier needs no introduction. Today, STOE’s prize was awarded to Nami Matsubura, a PhD student working in France, and the Elsevier prize to Joanna Wojnarska from Krakow, Poland. Both winners spoke well, clearly understood the science behind their ideas and described feasible projects. Matsubura’s project will be an extension of her PhD work, involving the synthesis and analysis of novel tellurates that might be used as components of electronic devices; she intends to use her prize for travel to a lab in Belgium. Wojnarska’s mainly computer-based project involves engineering novel non-centrosymmetric materials from highly symmetrical ‘building blocks’. Only the most promising molecules will be synthesised and crystallised.

The Dragons’ Den will be back on Saturday when the second set of candidates jostle to interest the dragons in their ideas. If you are reading this at the conference before then, that session is greatly recommended.

IUCr2017 Hyderabad: Blog Day 3, Wednesday 23 August: Collaborative Drug Development in India

Day 3, Wednesday 23 August: Collaborative Drug Development in India

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK

For many decades, India has been well-known worldwide for producing cheap, generic versions of essential medicines, in a valuable role that led it to be termed ‘the world’s pharmacy’. The Indian drug discovery industry is much newer, dating only from the 1980s, and if you see success only in terms of drugs registered by the FDA it has had very little. No novel compound discovered in India during the last thirty years has yet reached the market. The challenges currently faced by the Indian pharmaceutical industry, however, are mirrored worldwide and, as in many other countries, increasing collaboration between the various sectors of drug research – academia, government and industry – is seen as key to increasing productivity. This was the theme of an interesting and very well attended session in the IUCr parallel programme. The session focused on an area of research that is equally applicable in innovative drug research and generic drug development, that is a key strength of Indian science, and that has a strong association with crystallography: solid state forms in drug formulations.

With the designated session chair, G. Sahni from CSIR in New Delhi, absent ill, the session was chaired by Gautam Desiraju (IIS, Bangalore). His first task was to introduce himself as the first speaker, and he began by re-stating some of the problems with the Indian pharmaceutical industry in an era in which increased investment is leading to disappointingly few novel drugs on the market. In this context, research into novel drug formulations is a cheaper alternative that plays to India’s strengths in solid state and crystal chemistry. Drug compounds can exist in a variety of forms including salts, co-crystals, solvates and amorphous forms, and each of these can be polymorphic. There are many ways to alter the physical properties of a drug compound; the aim of drug developers is to move their most promising molecules into the so-called ‘golden region’ with high aqueous solubility but high membrane permeability. He ended his talk with an example; the antibacterials norfloxacin and sulfathiazole can be delivered as a mixture, but co-crystallisation will improve the permeability of the mixture without changing the efficacy of either compound.

Regulatory agencies have been involved in solid-state chemistry since the effects of crystal form on drug stability were first noticed in the 1960s. Steve Byrn, who has worked in industry and regulatory affairs and is now at Purdue University in Indiana, USA, explained how regulators approach these issues. He cited the example of the HIV protease inhibitor ritonavir, which was known for a time as the ‘magic Johnson drug’ for the dramatic improvements it offered to patients with AIDS. However, it formed insoluble spherulites in the soft gel capsules in which it was dissolved, reducing its bioavailability and thus its effectiveness. For a while, it was only available in a liquid form that tasted so bad that some patients quipped that they would rather die from AIDS. Some 80% of drugs currently under development have potential problems with solubility. Byrn described the concept of ‘equivalence’ that the FDA uses to determine whether forms of a product will behave in the same way. For two formulations to be equivalent they must have the same microstructure; a new drug polymorphism is not a generic but a novel entity.

With Dr Sahni absent, Professor A. Nangia, the director of the National Chemical Laboratory at Pune, India, gave an unscripted, largely autobiographical talk. He has worked in drug discovery in government and academia and as an entrepreneur, and he described the changes that he has seen in the research funding landscape in India throughout his 30-year career. Before the millennium, funding was low but safe; since then there have been ups and downs but on average there have been more funds available, and students recently graduating from his lab have gained experience with state-of-the-art equipment. Funding is also available for research-based startup companies, but there have been few genuine successes so far. A lively discussion focused on possible reasons for this, with the academic bias of the peer review process and the need for market ‘pull’ as well as technology ‘push’ emerging as likely reasons.

Dr A. Venkateswarlu from Dr Reddy’s Institute of Life Sciences (DRILS) in Hyderabad looked at the role of co-crystals in drug development from a manager’s perspective, starting by stressing the difference between drug substance (the active compound) and drug product (the finished tablet or capsule, in which that compound has been combined with other ingredients). Any molecule that alters the drug’s activity when combined with a drug substance – as co-crystal components may – is also considered a drug substance. He applied the well-established SWOT model (strengths, weaknesses, opportunities and threats) to pharmaceutical co-crystals. A different co-crystal form will sometimes offer a solution to problematic pharmacokinetics and can also add to intellectual property, although not to the same extent as a completely novel compound would. The final talk was entertaining, eclectic and entirely unscripted; the speaker, India Glycols’ R.K. Khandal, abandoned his slides saying that the material he had prepared had all been covered. A.V. Rama Rao, owner of contract research company Avra Laboratories in Hyderabad, summed up the session, stressing again the rewards and challenges of working in industry.


IUCr2017 Hyderabad: Blog Day 2, Tuesday 22 August:The salt of the earth

Day 2, Tuesday 22 August: The salt of the earth

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK

What links the history of crystallography, Gandhi, the Indian chemical industry and the Guinness Book of Records? Unless you keep an exceptionally strict diet, you have probably eaten some today. It is common salt, which most people will remember from high school by its chemical name: sodium chloride. This humble compound was the subject of the fascinating session that kicked off the IUCr Congress parallel programme. This programme has been designed to highlight aspects of crystallography and structural science that don’t fit into the rigid structure of plenaries, keynotes and micro-symposia that comprise the main event. ‘The salt of the earth’ fitted that bill extremely well.

Common salt was chosen as a session topic to celebrate, of all things, a world record: the largest model crystal structure ever built. Robert Krickl, a freelance science communicator from Vienna, Austria, spent a year of his life building a 3’ x 3’ x 3’ model of a salt crystal, with its constituent sodium and chloride ions represented by red and white balls. One third of this structure will be sitting in the HICC foyer throughout the meeting. Krickl gave the first talk, and he began by explaining the inspiration behind his model. He moved into science communication following a PhD in crystallography communication and had made something of a name for himself with travelling exhibitions by the International Year of Crystallography (IYCr) in 2014. Asked then to ‘do something about it’ he was single-handedly responsible for Austria’s second place in the table of countries’ involvement in IYCr, touring the country with an exhibition and giving presentations at 182 schools. His plan to build the largest-ever model crystal structure was announced at the very end of the IYCr closing ceremony.

The choice of sodium chloride was an obvious one for Krickl; his model was built in 2015, exactly 100 years after the father-and-son team of W.H. and W.L Bragg were awarded the Nobel Prize for determining the crystal structure of this compound. A century later Krickl set about the task of acquiring the 38880 coloured balls and over 10km of sticks that he needed. The final model has repaid all his hard work, intellectually if not yet financially. If you look into it from different angles you will see an astonishing range of beautiful, symmetrical patterns. It can be disassembled so small parts can be displayed in museums or taken into schools. And the 25th IUCr congress in 2020 will be held in Prague, only about 300km from Vienna. Krickl might take his complete structure there; or, perhaps, he could challenge delegates to build a more complex model there.

Each of the four talks that followed explored a different aspect of salt: in the history of India and of crystallography, in contemporary science and in industry. Dinkar Joshi, an expert on the life of Mahatma Gandhi, described the history of salt taxes in India under the British Empire as a background to Gandhi’s famous ‘salt march’ of 1930. At the time, Indian salt was taxed to encourage Indians to buy imported salt that had been brought in as ballast for ships. Gandhi had written to the Viceroy with 11 demands, one of which concerned the salt tax; when he received no reply, he chose the salt issue for his ‘satyagraha’ (civil resistance) because of its importance to all Indians. Twenty-eight marchers, ranging in age from Gandhi himself at 61 to his teenage grandson, marched for 24 days to gather salt illegally at the coastal village of Dandi in Gujarat; the rest is history.

Mike Glazer from the University of Oxford, UK, vice-president of the IUCr explained the role that sodium chloride had played in the Braggs’ discoveries. It was not the first compound to produce a diffraction pattern (of sorts) in a beam of X-rays; that honour had gone to copper sulphate, a few years earlier. It was, however, the first to produce a diffraction pattern that was good enough for a correct structure to be determined. Interestingly, potassium chloride (KCl), which has the same structure, produced a different type of diffraction pattern because potassium and chloride ions have the same number of electrons and were therefore ‘seen’ as equivalent by the X-rays. The Braggs’ structure showed sodium chloride to be a ‘pure’ ionic compound, less than 20 years after the discovery of the electron. This was much to the chagrin of some chemists who had expected to see ‘molecules’ in the structure: but the rest, again, is history.

The final two talks brought the subject up to date. First, Artem Oganov, a solid state chemist with positions in both New York and Moscow, explained some of the properties that common salt’s ‘3D chessboard’ type cubic structure give to the many other compounds that share it. He took examples from centuries of solid state chemistry, taking the story right up to the present day and his own work. Among the structures he mentioned was a novel form of boron named gamma boron, in which small and large clusters of atoms replace the sodium and chloride ions on a cubic lattice; this is one of the hardest substances known. And finally, Amitava Das, director of an Indian government lab in Bhavnagar, described the vitally important role that common salt plays in the Indian chemical industry and thus in the country’s economy.


IUCr 2017 Hyderabad: Blog Day 1, Monday 21 August: International crystallography, collaboration and community

The opening of the 24th congress and general assembly of the International Union of  Crystallography

The opening of the 24th congress and general assembly of the International Union of Crystallography was marked by a splendid programme that stressed, time and again, the international nature of our crystallographic community. When Professor Gautam Desiraju, the organising committee chair and immediate past president of the IUCr, quoted one of the discipline’s founding fathers, W. L. Bragg, in his welcome address: “At a scientific conference nationality disappears” he could have been summing up the whole event.

Certainly, this is the most diverse IUCr congress yet, as Desiraju explained. There are representatives of 73 countries here in Hyderabad, more than the 58 national members of the International Union. India is represented by over 500 delegates and the other BRICS countries – Brazil, Russia, China and South Africa – have all sent substantial delegations. The challenges and opportunities for scientists in these very different but in many ways surprisingly similar emerging countries will be discussed later in the week. Several countries including the Cameroon and Myanmar have sent a single delegate, but the most significant example of the ‘borderless’ nature of crystallography might be the 17 delegates from Bangladesh. Three of these are students who have joined the band of enthusiastic conference volunteers on equal terms with their domestic counterparts.

The IUCr President, Marvin Hackert of the University of Texas, Austin, gave a talk running through the history of the Union and its congresses. Like independent India, the IUCr was ‘born’ in 1947, and its international congress has taken place every third year since 1948. It has grown out of recognition since those early days but its basic roles are essentially unchanged: maintaining standards, publishing books and journals (including the International Tables) and promoting international collaboration. And a number of new initiatives have been started in or after the highly successful International Year of Crystallography in 2014. These include the LAAMP project – or the Lightsources for Africa, the (Southern) Americas and Middle East Project – to provide greater access to advanced synchrotron sources for scientists working in these disadvantaged regions. India already has two such sources, with others planned.

Paul Peter Ewald, a pioneering crystallographer known to students of structural science throughout the world for his ‘Ewald sphere’, was one of those principally involved in setting up the IUCr. Since 1986, his memory has been honoured by the award of the Ewald Prize at each congress to a distinguished crystallographer. The 2017 prize was therefore the eleventh in the series; it was awarded to Sir Tom Blundell from the University of Cambridge, UK, a pioneering structural biologist and a co-founder of Astex Pharmaceuticals.

Blundell’s prize lecture was a tour de force, a whirlwind summary of half a century at the forefront of structural biology. Time and again, he came back to the importance of collaboration, both between nationalities and between academic and industrial scientists. And time and again he came back to his mentor, Nobel laureate Dorothy Hodgkin. He joined Hodgkin’s lab as a student in 1964, the year in which she won the Chemistry Nobel, and became a member of the group that solved the 3D structure of insulin. He described giving his first plenary lecture at an international conference as a 27-year-old in 1969, showing delegates at the eighth IUCr congress the newly-solved structure of that vitally important biological molecule.

During his talk, he drew out four ‘lessons’ from Dorothy Hodgkin’s example and the insulin story, illustrating them with anecdotes from throughout his career.  Firstly, he explained that good science requires a long-term vision by citing the thirty years between the first insulin crystals and the first publishable 3D structure. There are lessons here for today’s grant agencies and journal editors. His second point stressed the value of international and interdisciplinary teams and his third the importance of writing up experimental methods: Protein Crystallography, the book he co-authored with Louise Johnson in 1976, was the first authoritative textbook on this subject.

Blundell devoted most time to the fourth ‘lesson’, on the value and quality of industrial science. He has collaborated with the pharma industry since the Seventies – then perhaps rather improbably as a left-wing firebrand of an Oxford City councillor. His was one of the groups that simultaneously solved the structure of HIV’s protease, paving the way for some of the most successful drugs for AIDS. In 1999 he and two ex-colleagues, Harren Jhoti and Chris Abell, founded Astex to pioneer the technique of fragment-based drug discovery. This company is now wholly owned by Otsuka Pharmaceuticals in Japan, and eighteen years after the program was launched, its first drug, riboclicib, has just received FDA approval for breast cancer. Dorothy Hodgkin herself would recognise this time-scale. Blundell is now taking the technologies pioneered at Astex back into academia for complex targets and neglected diseases, the latter with generous funding from the Gates Foundation. Despite passing the ‘official’ retirement age he still has plenty of plans for his international, interdisciplinary team, and for what his mentor might have called ‘useful’ crystallography; I will be reporting on more of both throughout the meeting.

Dr Clare Sansom, Department of Biological Sciences,  Birkbeck College, London, UK