Category Archives: Medical research

Medical research

Top 20 books: discovering worlds

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Artist's conception of a hypothetical planet covered in water around the binary star system of Kepler-35A and B.

Artist’s conception of a hypothetical planet covered in water around the binary star system of Kepler-35A and B.{credit}NASA/JPL-Caltech{/credit}

In terms of job satisfaction, discovering worlds must take the Sachertorte. Sibling astronomers William and Caroline Herschel, for instance, rejoiced in a haul that included Uranus, eight comets and several moons gleaned from what William called the “luxuriant garden” of the skies. Their final tally of deep-sky objects, with that of William’s gifted son John, numbered in the thousands. I’m sure their minds would be boggled by today’s exoplaneteering exploits — such as the TRAPPIST-1 system of seven Earth-like planets that fully emerged this year.

In my way, I’m in the business of discovering — and rediscovering — worlds. That they’re between two covers and on sale in your local bookshop is neither here nor there. And the 2017 harvest has been rich. We revisited Jonathan Swift’s 1726 Gulliver’s Travels, for instance — which, Greg Lynall noted in his eye-opening essay, is a journey across an unfamiliar Earth that even features Swift’s accurate prediction of the moons of Mars, 150 years before their detection. (The terra incognita flavour of this year’s events gave all that particular resonance.)

As for the new books sifted from the non-stop stream, as always I entered their portals with the open mind of an explorer. Thus, through Caspar Henderson’s A New Map of Wonders we scope the known cosmos with new eyes. In Hetty Saunders’s My House of Sky we sift the psyche of reclusive nature writer J.A. Baker. And in Jonathan Silvertown’s Dinner with Darwin, we see a plateful of food transformed into a repository of dazzling evolutionary stories.

It has, in short, been an astounding year for those of us engaged in tracking literary planets across the publishing firmament. Here’s my sky survey.

Improbable Destinies, Jonathan Losos. Riverhead. In a “deep, broad, brilliant” study, the biologist explores how evolutionary solutions, morphological to molecular, repeatedly emerge. (Reviewed here.)

A Crack in Creation, Jennifer A. Doudna and Samuel H. Sternberg. Houghton Mifflin. A pivotal player in the CRISPR saga delivers her dispatch from the genome-editing frontline. (Reviewed here.)

Collecting the World, James Delbourgo. Allen Lane. A life of Hans Sloane — medic, Royal Society president, ‘wondermonger’ and collector extraordinaire — is limned by an accomplished historian. (Reviewed here.)

The Death Gap, David Ansell. University of Chicago Press. The social epidemiologist lays bare how ‘structural violence’ in US healthcare fosters disparities in life expectancy. (Reviewed here.)

The Great Leveller, Walter Scheidel. Princeton University Press.  In a magisterial socio-political chronicle, the historian untangles the deeper roots of inequality. (Reviewed here.)

The Imagineers of War, Sharon Weinberger. Knopf.  The defence writer delves into the shadowy history of DARPA, the US agency that forecasts “imagined weapons of the future”. (Reviewed here.)

Miracle Cure, William Rosen. Viking. The accomplished writer’s swansong superbly captures the rise of antibiotics, from the discovery of penicillin on a mouldy cantaloupe to the war on resistance. (Reviewed here.)

The Vaccine Race, Meredith Wadman. Viking. A former Nature journalist tells the convoluted story of human fetal cell line WI-38, still deployed in vaccine research. (Reviewed here.)

Deep Thinking, Garry Kasparov. PublicAffairs. The chess titan revisits his 1997 match against computer Deep Blue in an “impressively researched” history of AI. (Reviewed here.)

The Songs of Trees, David George Haskell. Viking. In a sensory tour de force, a biologist documents the exquisite interconnections of arboreal life. (Reviewed here.)

Rigor Mortis, Richard F. Harris. Basic Books. The science journalist jumps into the deep end of biomedicine’s reproducibility crisis. (Reviewed here.)

Dawn of the New Everything, Jaron Lanier. Bodley Head. The virtual-reality pioneer traces the unconventional trajectory of an extraordinary career. (Reviewed here.)

The Origins of Creativity, E.O. Wilson. Liveright. In exploring the wellsprings of creativity, the ecologist calls for a “third enlightenment” meshing science with the humanities. (Reviewed here.)

Outside the Asylum, Lynn Jones. Weidenfeld & Nicolson. A psychiatrist working in war and disaster zones elucidates both policy implications and the uncommon courage of survivors. (Reviewed here.)

The Quantum Labyrinth, Paul Halpern. Basic Books. A physicist unpicks the intertwined lives of consummate theoreticians and chums Richard Feynman and John Wheeler. (Reviewed here.)

Life 3.0, Max Tegmark. Knopf. The cosmologist peered into possible risks and benefits of evolving AI, from an autonomous-weapons arms race to quark-powered ‘sphalerizers’. (Reviewed here.)

A Mind at Play, Jimmy Soni and Rob Goodman. Simon & Schuster. A journalist and a political theorist vividly portray information theorist — and rocket-powered-Frisbee inventor — Claude Shannon. (Reviewed here.)

Stalin’s Meteorologist, Olivier Rolin. Harvill & Secker. A harrowing account of a Soviet researcher exiled to the Gulag testifies to the endurance of science in the midst of political chaos. (Reviewed here.)

The Darkening Web, Alexander Klimburg. Penguin. The policy expert reports on the new cold war between ‘free Internet’ and ‘cybersovereignty’ forces. (Reviewed here.)

The Seabird’s Cry, Adam Nicolson. William Collins. The environmental writer’s inspired survey of 10 seabird species — albatross to shearwater — is a paean to life at the edge. (Reviewed here.)

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

Superbugs: fighting the flood of antimicrobial resistance

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Enterobacter cloacae, Enterococcus faecalis, Staphylococcus epidermidis and the Superbugs exhibition.

Petri dishes with cultured Enterobacter cloacae, Enterococcus faecalis, Staphylococcus epidermidis and Escherichia coli at the London Science Museum’s Superbugs exhibition.{credit}® The Board of Trustees of the Science Museum{/credit}

Antimicrobial resistance has spread to London this month. The source of the outbreak? The Science Museum: its new exhibition, Superbugs, explores this monumental issue and our responses to it.

As Superbugs graphically shows, the inflammatory tone of the many headlines predicting an impending antibiotic apocalypse is not baseless. The evolution and spread of resistance among serious (and increasingly commonplace) bacterial infections continues to blunt much of our antibiotic arsenal, and make routine operations significantly more risky. Such infections now claim almost 700,000 lives annually, a figure that could rise to more than 10 million by 2050.

Superbugs isn’t out simply to scare, however. Much like Nature Microbiology, the journal I edit, the Science Museum aims to join the ‘resistance against resistance’ by shining a light on the problem’s scale, and the range of potential solutions.

The monumental 'wall' and towers at the exhibition.

The monumental ‘wall’ and towers at the exhibition.{credit}{credit}® The Board of Trustees of the Science Museum{/credit}{/credit}

The physical design of the installation aptly reflects aspects of the crisis. A vast illuminated wall dominates; set into it is a series of displays. This monolith, emblazoned with the show’s title, speaks of antibiotics’ barrier function — how they act as a great dam holding back a flood of infections. Standing in front of this cracked levee are 12 small towers into which have been set Petri dishes. Each contains a different type of (inactive) microbe, including MRSA and Neisseria gonorrhoeae — like outposts of resistance that have breached the barricade and now mingle among the crowds. It’s a powerful scene.

I was drawn irresistibly to the inset display cases. Combining text with striking visuals and interactive content, these take the visitor through medical history, from the discovery and introduction of antibiotics in the first half of the twentieth century, to the rise of resistance in the years following the introduction of each new drug, to ongoing efforts to revitalize our dwindling drug cabinet. Peppered through are personal testimonies. We meet doctors explaining why antibiotics are overprescribed; a nurse reminding of the fundamental importance of their work on infection control; designers who create products that enable no-touch use, or incorporate anti-bacterial materials, to reduce the risk of transmission.

Interviews with nurses, medics and others waging war on antibiotic resistance feature in the exhibition.

A display on the people at the frontline of ‘resistance against resistance’.{credit}® The Board of Trustees of the Science Museum{/credit}

We hear a recording of bacteriologist and discoverer of penicillin Alexander Fleming, describing how microbes can become ‘educated’ to resist a drug. A culture of Penicillium mold grown from a stock of his original sample is shown nearby. A video describes the harrowing experience of Geoffrey Pattie, a cancer patient who during surgery contracted a strain of Klebsiella pneumoniae resistant to all current antibiotics. He spent five months in an isolation ward, and today lives with the life-altering effects of the infection, such as reduced mobility.

Nearly half of antibiotic use occurs in agriculture, to treat and prevent infection in livestock, but often also to promote growth. The drugs and bacterial resistance genes that they select for become widespread in terrestrial and marine environments, giving a large potential reservoir from which resistance can leap into clinically relevant pathogens. Inevitably, that is a serious problem for human health. The show reveals some of the technological fixes that are being investigated, including automated systems for monitoring livestock welfare to allow targeted interventions rather than treating an entire herd prophylactically. Also presented are possible alternative approaches to tackling infections, such as phages (viruses that kill bacteria) sourcing new antibiotic leads from oceans, soils and host-associated microbiomes in humans, komodo dragons and leafcutter ants.

The promise of such efforts is stirring. But finding a new antibiotic class that will make it to the clinic is “like searching for a needle in a field of haystacks”, cautions one researcher interviewed.

The bacteria leafcutter ants use to defend their nests against fungi and microbes excrete chemicals that are effective antibiotics.

The bacteria leafcutter ants use to defend their nests against fungi and microbes excrete chemicals that are effectively antibiotics.{credit}® The Board of Trustees of the Science Museum{/credit}

What isn’t covered in much depth is the parlous state of the antibiotic R&D pipeline. Many large pharmaceutical companies have closed their antibiotic development programmes in recent years. That includes Pfizer, the main sponsor of the exhibit — although the company did announce in 2016 that it planned to acquire AstraZeneca’s antibiotics division, and reinforced a strategic focus on tackling infectious diseases. The economics of antibiotic discovery and development is complicated: to bring a drug to market takes a massive investment in time and finances. Yet we will need these new drugs to be used ever more sparingly in future. So, under the current system, there is actually a disincentive for industry to put in the necessary investment – they would never break even, let alone see a return.

Superbugs is doubly timely. This week (13-19 November) is the World Health Organization’s World Antibiotics Awareness Week 2017, an opportunity to take stock of progress. Antibiotic resistance, until recent years a concern only of clinicians and microbiologists, is now globally recognised as a crisis through the work of key individuals, such as Britain’s chief medical officer Sally Davies, and reports from national and international bodies. In 2016 this culminated in the UN High-Level Meeting on Antimicrobial Resistance (see this Nature Microbiology editorial).The rise in academic research and conferences focused on antimicrobial resistance is a positive sign that new approaches can and will be found, despite the issues with the pharma marketplace and the ongoing hunger for antibiotics in agriculture and medicine.

But we remain a long way from winning what the Science Museum describes succinctly as the “fight for our lives”. Hopefully this polished, fact-packed exhibition will call many more to arms — from the lay visitor to the family doctor, local farmer and political representative.

Andrew Jermy is chief editor at Nature Microbiology. He tweets at @jermynation.

Superbugs: The Fight for Our Lives is free, and at the Science Museum until spring 2019.

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

Women in Medicine: opening the clinic door

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Flic Gabbay, xxx, next to a bust of xxx.

Flic Gabbay, co-founder of the Society for Pharmaceutical Medicine, next to a bust of Cicely Saunders, founder of the hospice movement.{credit}John Chase (c) Royal College of Physicians{/credit}

Visitors stepping into the Royal College of Physicians (RCP) in London are normally greeted by the sombre stares of imposing men, in portraits lining the walls. From today, women outshine them, in 26 photographic portraits of modern female clinicians ranged along the central stairwell. Each holds an image of a historical figure who inspired them.

The exhibition, Women in Medicine: A Celebration, comes as the RCP — which accredits UK physicians and represents over 30,000 doctors globally — readies for its 500th birthday in 2018. Over that time, it has had just three female presidents: unsurprising, given that women could not join until 1909.

The contemporary clinicians in the portraits are esteemed in their own right, and there is still plenty of trail left for them to blaze. But it is the historical photos that drew my eye.

Fiona Caldicott, xxx, holding a photograph of xxx.

Fiona Caldicott, a past president of the Royal Society of Psychiatrists, holding a photograph of pioneering psychiatrist Helen Boyle.{credit}(c) Oxford University Hospitals NHS Foundation Trust {/credit}

Recent years have brought a welcome spate of books, movies and exhibitions dedicated to honouring pioneering women in science. The best of these, like the book and film Hidden Figures, draw attention to forgotten achievements and struggles, and reveal a history that had, shockingly, gone untold. More often, such collections tend to sample from the same pantheon. And although Marie Curie and Rosalyn Franklin deserve their fame, I’m often left with the feeling that we are overlooking important contributions from others.

The RCP show steps outside this elite circle. Here is Helen Boyle, one of the first women psychiatrists in Britain, who led the charge for early diagnosis and treatment of mental disorders near the end of the nineteenth century. Holding her photo is Fiona Caldicott, a past president of the Royal College of Psychiatrists, and perhaps best known for her work on the 1997 Caldicott Report, a guidance document about protecting confidential patient information.

Jane Dacre, xxx

Jane Dacre, Royal College of Physicians president, with a photograph of pioneering hepatologist Sheila Sherlock.{credit}John Chase (c) Royal College of Physicians{/credit}

Jane Dacre, the current president of the RCP, selected physician Sheila Sherlock, who founded hepatology, the study of the liver. According to an online biography connected to the exhibition, Sherlock said that she opted to study that organ because “no one else was doing it”.

All these women racked up notable achievements — and overcame tremendous obstacles to do so. But too many of the write-ups on the accompanying website read like CVs: it is sometimes difficult to glimpse the person behind the achievements, no doubt due to limited space and historical records. Still, there is plenty to whet the appetite. For example, I’m eager to learn more about the friendship with a dying man that led Cicely Saunders to found the modern hospice movement.

Asha Kasliwal, xxx, holds portrait of xxx in the Women in Medicine exhibition at the xxx.

Asha Kasliwal, president of the Faculty of Sexual and Reproductive Healthcare, with a photograph of Anandibai Gopal Joshi, one of the first women in India to study Western medicine.{credit}(c) FSRH{/credit}

Happily, the exhibition’s brief biography is enough to reveal why Anandibai Gopal Joshi — among the first Indian women to practice Western medicine — chose to enter medicine. Married at age 9 and a mother at 14, Joshi’s child died ten days after he was born due to inadequate medical care. “My soul is moved to help the many who cannot help themselves,” Joshi wrote in her application to the Women’s Medical College of Pennsylvania. (Her photograph is held by Asha Kasliwal, who trained in Mumbai and is now president of the Faculty of Sexual and Reproductive Healthcare.)

For perspective, a trip downstairs to the Treasures Room, featuring medical tools from past centuries, is fascinating. Among them is a ‘modesty doll’. In a time when clinicians were all men, women would point to areas on the doll corresponding to the body part in question to describe their symptoms.

In a nearby display case hangs the ornate formal robe, heavy with real gold thread, of the RCP’s president, next to a photo of Dacre wearing it. The robe cannot be shortened, and positioning it on Dacre’s petite frame took some doing. Yet you’d never know it: it fits her perfectly.

Heidi Ledford is a reporter for Nature in London. She tweets at @heidiledford.

Women in Medicine runs at the Royal College of Physicians until 19 January 2018.

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

An immortal life: Henrietta Lacks on film

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In the HBO film based on Rebecca Skloot’s book of the same name, Oprah Winfrey plays Henrietta Lacks’ daughter Deborah Lacks.

The idea that people should have a say over how their cells are used in research isn’t revolutionary, but it flies in the face of research practices over the past century. That it nearly became law is due in no small part to Rebecca Skloot’s 2010 bestseller The Immortal Life of Henrietta Lacks, the story of the African-American woman living in Baltimore, Maryland, whose fatal tumour – taken by scientists at Johns Hopkins Hospital in 1951 without the knowledge or permission of Lacks or her family — gave rise to the first immortal human cell line, HeLa.

The book fuelled a much-needed conversation about scientists’ moral obligations to research participants and their families. Now a powerful film adaptation of the same name, starring Oprah Winfrey as Lacks’ youngest daughter Deborah, looks set to amplify that.

Skloot’s book covered a lot of ground, and the film’s director George C. Wolfe (best known for directing and producing Broadway hits such as Tony Kushner’s Angels in America) does an admirable job cramming in details about how HeLa cells were established and their ongoing impact on research. But the movie, broadcast on 22 April on premium US television network HBO, largely covers the decade it took for Skloot to report and publish her book. It focuses in particular on her efforts to gain the trust of Lacks’ family and build an emotional bond with Deborah Lacks.

Their relationship can feel overly dramatized, although Wolfe should not be faulted for taking some dramatic licence with Skloot’s book in what is, after all, a dramatisation (she also served as an executive producer). But much of the film rings true. A scene in which Deborah Lacks questions Skloot’s financial motives and grabs her arm is exactly as described in the book.

Deborah Lacks.

Deborah Lacks.{credit}Rebecca Skloot{/credit}

By omitting some key aspects of the book — the science and history of cell culture and large swathes of Lacks’ biography — the film can feel meta. It is, after all, a film based on a book about a journalist trying to write a book. But it should encourage more people to read the story and absorb its powerful message of social injustice institutionalized by science.

US National Institutes of Health (NIH) director Francis Collins and then-deputy Kathy Hudson have noted that Lacks’ story inspired policy changes in the rules that govern research on human subjects (officially known as the Federal Policy for the Protection of Human Subjects, but widely known as the Common Rule). “The people who are participating in research and providing pieces of themselves should be providing permission as well,” Hudson told Nature in 2015, when the government floated a proposal that would have required them to get approval to reuse discarded samples of blood, urine and other specimens for studies beyond those the subject initially agreed to. But the proposal caused consternation among many scientists. They breathed a sigh of relief this year, when the  final version. of the Common Rule largely maintained the status quo. As long as a participant’s name is removed from the sample, scientists needn’t obtain new consent.

Henrietta Lacks.

Henrietta Lacks.{credit}Courtesy of the Lacks family{/credit}

That may seem like a setback in a quest for justice the Lacks family is all too familiar with. But other developments suggest that the Lacks’ story has changed how research participants are treated by scientists.

Currently, a movement for “dynamic consent” — focused on the establishment of a lasting relationship between researchers and study participants — is growing. It was pioneered by professor of health, law and policy Jane Kaye, while elements of it are being used in Australia. Participants or their relatives (in cases where they are no longer alive) are kept up to date on how their samples are used in research, and they can opt out of particular studies or remove their sample entirely.

The Lacks are finally gaining some control over HeLa cells, if not the remuneration many members have in the past and some still seek. In 2013, after researchers funded by the NIH sequenced the HeLa cell genome without the knowledge or consent of the Lacks family, Collins helped broker a deal with the family to limit access to the data. Now, all NIH-funded scientists and others who want the best quality HeLa genome must explain their research to a committee that includes a Lacks family member. It’s enough for a sequel.

Ewen Callaway is a senior reporter for Nature based in London. He tweets at @ewencallaway. 

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

A requiem for recollection

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Elegy-logo-and-title-treatment-NEW2The best science fiction can predict the science of tomorrow and colour the preoccupations of today. It’s too early to tell whether Nick Payne’s new play, Elegy, will do the former, but it certainly takes a powerful swing at the latter.

Payne’s short three-hander, currently at the Donmar Warehouse in London, evokes the challenge of coping with a relative with worsening dementia, a dilemma well-known to many families. The sci-fi twist comes in the form of a new therapy that carries a heavy cost.

We meet a couple in their sixties. Lorna (Zoë Wanamaker) has an unnamed disease, which has taken its toll on her mood and memory. She and partner Carrie (Barbara Flynn) have to decide whether to embark on a radical new treatment, or let her condition continue its march.

In Payne’s world, doctors can map the brain’s tangle of neurons and have learned how to replace some ailing circuits with prosthetic versions. Normal functions such as walking can be preserved or restored. But, the couple is told, the treatment will not be able to reinstate memories from a large chunk of the patient’s adult life: the period during which the couple met and married. Lorna will have to sacrifice a life’s worth of memories with Carrie for a healthy post-op life.

Some of the science fiction has a basis in today’s fact. Neuroscientists are working on the brain’s ‘connectome’ — a map of all the brain’s neural projections. But they are nowhere close to having a complete atlas, let alone a definitive guide of what functions and memories lie where. It’s also unlikely that Lorna’s  surgery would selectively remove memories depending on their age, although one 2009 study suggested that different brain regions help recall memories of different ages.

Patients today have dire choices similar to this. People with Parkinson’s, for instance, might have to choose between a drug with severe side effects, a major operation or a worsening of the movement disorder. But in Elegy, Payne presents a different type of Hobson’s-choice: would you change your ‘self’ to save your life? As Lorna asks, “What life, if it isn’t this life?”

Nina Sosanya and Zoe Wanamaker in Elegy by Nick Payne.

Nina Sosanya and Zoë Wanamaker in Elegy by Nick Payne.{credit}Johan Persson{/credit}

One speech mars the flow. The doctor, Miriam (Nina Sosanya), gives the couple a primer on axons and glutamate that seems lifted from a neuroscience textbook. There are, rightfully, no more such explications. But there are inconsistencies in how we are told the treatment works and what neuroscientists know about how the brain makes memories and stores motor programmes. A more profound integration of neuroscience into the plot might have helped that.

For instance, the therapy Miriam offers — which excises memories that cannot be replaced — is problematic. Memories do not exist in one neural area; they are stored more widely. Likewise, many motor procedures are essentially glorified memories: riding a bike is a classic example. It’s not clear that these would live somewhere entirely and conveniently different from Lorna’s recollections of events in her life.

But the premise needn’t make neuroscientific sense for the plot to touch us. And it does, in part because the characters are so well-portrayed. Wanamaker shows us Lorna’s deterioration viscerally — walking across the stage and wheeling around angrily when she forgets what she wanted there — as well as her struggle to adjust to healthy life after the procedure. Sosanya brings a humanity to Miriam, despite the scientific soliloquies. She also gets to crack a science joke, raising a laugh from the audience when she tells the couple that the treatment works in mice, rats…and zebrafish.

Zoe Wanamaker in Elegy.

Zoë Wanamaker in Elegy.{credit}Johan Persson{/credit}

The play’s structure and dialogue also reflect the fragmentation of Lorna’s memory and the couple’s life together. We start at the end of the story, when Lorna has already undergone treatment, and look back at the beginning of their relationship, their appointments with the doctor and struggle to cope with Lorna’s dementia. The splicing and disjointedness force you to work to figure out where each scene fits and what has come before, evoking the confusion of the condition.

The dialogue is wonderfully natural, yet also crafted to add to the sense of fragmentation. Barely any character finishes a sentence and many important words are missed out, just as people talking about difficult subjects will tail off and let the listener fill in the blanks. “I worry we’re in danger of reducing an extremely complex…” says Miriam, leaving the thought hanging under a barrage of questions from the couple.

In the middle of the stage, a tall tree trunk with a deep split along its length stands in a glass box. When Lorna’s memory clouds, the box fills with smoke. Like the sparse stage and the half-sentences, it is beautiful, disturbing — and memorable.

Kerri Smith is Nature’s podcast editor. She tweets at @minikerri.

Elegy runs at the Donmar Warehouse, 41 Earlham Street, London, through 18 June.

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

 

 

 

 

The Emperor of All Maladies, redux

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One of the remarkable features of Siddhartha Mukherjee’s Pulitzer Prize-winning history of cancer, The Emperor of All Maladies (2010), is its philosophical acuity. “Science embodies the human desire to understand nature; technology couples that desire with the ambition to control nature,” he writes. Cancer treatment is at the very edge of technological possibility, intervening in a disease that is our “desperate, malevolent, contemporary doppelganger”. To Mukherjee, cancer was not something, but someone.

Emperor

{credit}PBS{/credit}

Cancer: The Emperor of All Maladies, a three-part documentary, adapted from Mukherjee’s “biography” and directed by veteran filmmaker Barak Goodman, airs on PBS (the US Public Broadcasting Service) starting 30 March. It stands witness to the achievements of cancer research, but is also visceral and emotional.  Executive producer and co-writer Ken Burns, best known for his documentary series on the American Civil War and the Roosevelts, is adept at evoking empathy for those who feature — parents with sick children, wives learning of husbands’ prognoses, doctors faced with unspeakably difficult choices.

The structure hews closely to the book’s. Part 1 traces the disease to an ancient Egyptian record telling of an illness for which “there is no cure”, to rudimentary treatments that evolve from antiquity to modernity, to the mid-twentieth-century US “war on cancer”, for which pathologist Sidney Farber and socialite and philanthropist Mary Lasker galvanised support. Part 2, “The Blind Men and the Elephant”, looks at the shift towards piecing together the still-muddled puzzle of cancer genomics. It is proof of the progress over the past few years that immunotherapeutics, which Mukherjee’s book did not discuss, closes the series’ finale, “Achilles Heel”.

Yet as medicine advances on the screen, a subtler kind of progress can be detected in the voices of those whom cancer has touched. In 1978, essayist Susan Sontag, diagnosed with leukaemia, wrote in Illness as Metaphor of a peculiar sociological phenomenon — the “magic power” even the diseases’ names seem to hold. Until the AIDS epidemic of the 1980s, cancer evoked a uniquely potent dread. Some oncologists even avoided telling patients they were ill, a practice that still goes on in some parts of the world. When cancer could not be fully understood and confronted, it demoralized.

The most profound aspect of Burns’s visual rendering of Emperor of All Maladies is that it allows us to see the clarity that cancer research has brought about. We can now read the mutations of an oncogene, and look with astonishing precision at where a tumour has formed. In the last two years, as the series shows, work by Steven Rosenberg on T-cell therapy and James Allison on targeted tumour recognition has revealed how harnessing the immune system can combat cancers.

Such advances have divested cancer of some of its slippery, amorphous capacity to invoke terror. “Cancer, we have discovered, is stitched into our genome,” writes Mukherjee. “Perhaps [it] defines the inherent outer limit of our survival.” Burns’s documentary ends with “tempered optimism”, speculating that one day soon the disease will be managed “like any chronic illness”. For now, at least we have reclaimed our agency in facing it.

Cancer: The Emperor of All Maladies runs from 30 March to 1 April on PBS.

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

Resistance: the movie

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Resistance Tweets-05

{credit}Uji Films{/credit}

At the age of 12, I was knocked off my bicycle by a car, resulting in a compound fracture to my right leg that required pins and an external cage to enable the bone to reset and the wound to heal. Antibiotic therapy kept the threat of infection at bay. Recently during childbirth my wife contracted an infection that, fortunately, was cleared in her and our new-born baby following a brief course of antibiotics.

In each case, resistance to those drugs could easily have led to death. Something that, like many of those interviewed in Resistance, an alarming documentary film by Michael Graziano, I find almost incomprehensible in the twenty-first century. Campus screenings in the United States last year have now been followed by a release on ITunes.

The film weaves often harrowing personal tales to tell the story of the rise and fall of antibiotics over the past 85 years. We hear from adults and children who have suffered from infection — for example, Jesse Beam, a teenager who contracted MRSA (methicillin-resistant Staphylococcus aureus) on a camping trip with his father. Some, like Jesse, survived with long term-health impacts; others, tragically, did not. We witness medical experts, such as Brad Spellberg from the Geffen School of Medicine at UCLA, their emotions clearly visible as their most powerful tools fail. Spellberg describes treating a woman in her twenties with leukemia who died after contracting Acinetobacter, which developed resistance to all of the antibiotics available.

A natural resource squandered

How have we squandered what one specialist rightly describes as a precious natural resource? Graziano takes us from the discovery of penicillin to the present day, showing how overuse of these wonder drugs has blunted their effectiveness to a point where we are now on the brink of a post-antibiotic era. He covers all the bases: overuse in medicine, where doctors still prescribe antibiotics to patients infected with viruses; overuse in agriculture, where antibiotics are still gratuitously used as growth promoters; a pharmaceutical industry that by its very structure has become inimical to the costly development of drugs that should be used only rarely.

Resistance paints a sobering picture, albeit a US-centric one. The challenges posed by antimicrobial resistance are global in nature and increasingly need to be dealt with internationally. The film also devotes too little time to those striving to develop solutions, such as people working on phage therapy or others mining drugs from previously unculturable bacteria.

Furthermore, in framing the ineffective government bodies, the agriculture industry and (to a lesser extent) overprescribing doctors as having gotten us into this mess, Graziano lets the public off the hook too easily. Why is it that in Denmark the agriculture industry took heed of public debate and voluntarily agreed to stop the use of antibiotics as growth-promoters, but in the United States and other parts of the world this hasn’t happened?

Graziano walks the line between covering the science in sufficient depth while delivering a narrative accessible to lay audiences. Hopefully this balance will ensure that the documentary is shown as widely as possible, in schools, on prime-time television, so that its message is heard clearly by the general public, the media who inform them and the politicians who represent them. Changing the way that we use antibiotics is hard, but it is a pill that we must all swallow.

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

Rare diseases and precision medicine on film

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Bea Rienhoff with US President Barack Obama.

Bea Rienhoff with US President Barack Obama. {credit}Hugh Rienhoff{/credit}

When US President Barack Obama introduced his $215 million precision medicine initiative early this month, he showcased his politician’s penchant for sharing the inspiring personal stories of extraordinary citizens. One story that might be familiar to Nature readers was that of Hugh Rienhoff and his daughter Beatrice.

Now two documentary film makers, Allen Moore and Kori Feener, are raising funds via Kickstarter to tell Bea’s story — of “a violin-playing, theatre-performing tomboy with a disease so rare, no one else in the world has it” (see below). (For what it’s worth, Hugh prefers to call what Bea has a “condition” because he does not want her to feel limited by the negative connotation of the word “disease”). Feener adds, “We also want to focus on family advocacy.”

The funding drive finishes, fittingly, on International Rare Disease Day — 28 February.

Hugh, a trained clinical geneticist, embarked on a quest to identify the genetic cause of a puzzling array of symptoms affecting Bea, such as fingers and toes that won’t uncurl all the way and an inability to put on much muscle mass. After reading, consulting, cloning Bea’s genes in his basement and enlisting the help of a major genome sequencing firm, Hugh eventually identified the cause: a mutation in the gene that encodes transforming growth factor-β3 (TGF- β3), one of a family of signalling proteins involved in development and cell differentiation. He has since been working with a group of researchers to study Bea’s version of the gene in mice (Bea has one named Almond Joy in her bedroom), and he has been collecting examples of other people who share similar genetic variants. His hope is to best understand what lies in store for his daughter as she grows older. It is a profound example of what a parent might be able to do given the right tools, support and knowhow.

https://vimeo.com/115936139

Such stories have undeniable power. And resonance: much of Hugh’s diagnostic odyssey is familiar to parents who have bounced from doctor to doctor hoping to hear something other than “We just don’t know”.  Nicole Boice, inspired by these experiences, founded a rare-disease advocacy organization called Global Genes in Aliso Viejo, California, in 2008. “That sense of isolation is very common: the impact on the family on finances, dealing with insurance and finding someone who cares about this from a scientific perspective.”

Sharing the insights

Global Genes has a useful collection of documentaries and dramas recounting similar stories. It includes what many consider the prototype: Lorenzo’s Oil, George Miller’s 1992 film about Augusto and Michaela Odone’s quest to find a treatment for their son’s adrenoleukodystrophy, a fatty acid storage disorder that affects the nervous system. Tom Vaughan’s 2010 drama Extraordinary Measures tells the story of John and Aileen Crowley, who quit their jobs to found a biotech company in order to find a cure for the neuromuscular condition Pompe’s disease, which affects their two children. It’s inspiring — and fun, starring Harrison Ford as a brilliant but acerbic scientist. (Think Han Solo with a pipettor.)

The list also features recent documentaries showing how families and patients affected by rare diseases such as progeria, a rare disorder with symptoms that resemble accelerated aging (Life According to Sam), and the lysosomal storage disease Neiman-Pick Type C (Here.Us.Now.), are becoming more empowered, engaging with the science and taking their future into their hands.

International Rare Disease Day is a moment to raise awareness of under-the-radar conditions that don’t have huge support groups, research associations or lobbying arms. The White House initiative is slated to use genome sequencing on a cohort of 1 million Americans to further assess its value in delivering the right treatments, and it may ultimately enhance that awareness.

Although in Hugh’s eyes Bea will always be one of a kind, he knows there are others like her. Scientists have already uncovered at least three other individuals with mutations in the same gene, and they may help to provide guidance in keeping Bea healthy. “The truth of the matter is, there’s going to be a whole category of people: onesies and twosies and threesies of the genetics world. And that number of people will only grow.”

 

For Nature’s full coverage of science in culture, visit www.nature.com/news/booksandarts.

 

Robert Langer

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Massachusetts Institute of Technology, USA

A bioengineer sees a future for safe gene-silencing therapies.

The possibility of treating genetic disorders by modifying gene expression has been an attractive yet elusive goal for decades. Problems with the safety and efficacy of various types of gene therapy have held back progress. In particular, there have been some high-profile failures, including a number of deaths during clinical trials.

But seminal studies reported by Andrew Fire and Craig Mello in 1998 led to a potentially new class of therapeutic agent. These researchers, who went on to share a Nobel prize for their work, found that small pieces of RNA, dubbed siRNAs, can silence genes.

Although switching off genes may have fewer complications than adding new ones, the safe and effective delivery of genetic agents remains a critical challenge. I was therefore pleased to see a recent paper reporting tests of an siRNA-delivery system in monkeys (J. Heidel et al. Proc. Natl Acad. Sci. USA 104, 5715–5721; 2007), suggesting that safe, repeated systemic administration of siRNAs is possible.

Mark Davis of the California Institute of Technology in Pasadena and his colleagues created nanoparticles composed of siRNAs and a novel polymer based on the sugar cyclodextrin. These particles were injected into the monkeys and their health was monitored. The monkeys tolerated multiple doses of siRNA of increasing amounts.

This paper was of interest to me not only because my group works on lipid formations that might serve as delivery systems for siRNA or other genetic agents, but also because I was pleased to see a former student doing well. Jeremy, the first author, once worked in my lab as an undergraduate.

Studies such as this one are bringing back to the field the excitement that surrounded gene therapies in the 1980s.

Jeffery W. Kelly

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The Scripps Research Institute, La Jolla, California, USA

A biochemist considers whether protein misfolding plays a part in type II diabetes.

Much of my research is on cellular protein folding, and in particular on how protein misfolding or protein aggregation causes disease. My group has developed therapies for a spectrum of misfolding diseases, most of which are associated with neurodegeneration, such as Alzheimer’s.

But we are beginning to appreciate that therapies that affect protein folding could have a role in treating a much wider spectrum of diseases than is currently realized.

A compelling article from Gokhan Hotamisligil and his colleagues at Harvard University (U. Özcan et al. Science 313, 1137–1140; 2006) presents one example. They found that mice that are both obese and diabetic benefit from treatment with drugs that enhance protein folding.

Their experiment was motivated by observations that linked obesity and diabetic insulin resistance to stress in the endoplasmic reticulum (ER), a compartment in cells where a third of all proteins are folded.

The researchers gave their fat, diabetic mice chemicals that enhance protein folding in the ER. The effect was notable: the mice’s blood-sugar levels fell, they showed increased glucose tolerance and reduced lipid accumulation in the liver.

This suggests to me that protein misfolding may be at the heart of type II diabetes, the age-related disease for which these mice are a model.

Folding of the insulin receptor is inefficient. So it seems reasonable to speculate that cells could become insulin-resistant because of compromised insulin-receptor folding in the ER.

We may find, as we develop more selective small molecules to enhance ER folding, that we discover other disorders that can be treated in this way.