The Oxford Scientist: Challenges (#4)

MICHAELMAS 2018 • ISSUE 3

IMPACT

CHALLENGES

A New Eye for an Old Who do Eye I think you are?

New Oxford research aims to

help patients affected by eyesight The loss.science of first impressions

Welcome to the Tetris the Lab Smartin City The surprising between A tour around link the city of the PTSD and tetris future.

Mirror, Mirror Bac(teria) the A reflection on oneto of the most important innovations in hufuture

man history.

Using phage therapy to combat antibiotic resistance

OXSCI STAFF

OSPL STAFF CHAIRMAN

EDITOR-IN-CHIEF

Olivia Shovlin

NEWS EDITOR

Laura Hankins PRINT EDITOR

Laura Steel

WEB EDITOR

Jack Feltham

Daanial Chaudhry MANAGING DIRECTOR

Varsia Desselberger FINANCE DIRECTOR

Kavya Desphande TECH DIRECTOR

Antonia Siu

STRATEGIC DIRECTOR

Harry Gosling

COMPANY SECRETARY

HILARY 2019 • CHALLENGES

CONTENTS

4 EDITORIAL 5 6 8 9 10 12 13 14 15 16 19

What will it take to feed the world in 2050?

MATT JORDAN

Serena Parekh

Copyright © The Oxford Scientist 2018

Pore over this - advances in DNA sequencing NICOLE HASLER Who do I think you are? The science of first impressions CAITLIN ASHCROFT A universal blood test for cancer HARRIET HARDY The surprising link between PTSD and Tetris PRATIBHA RAI Using ultrasound to improve cancer treatment JONATHAN VINCE Spotlight - Dr Martine Abboud Worst journey, winter journey NOAH HEARNE

The mini-project microcosm of Hofstadter’s butterfly MARIA VIOLARIS Why is chaos so chaotic?

ARLENE LO SCHOOLS COMPETITION WINNER

The Science of a chilli

20 22 24 26 28 29 30

Bac(teria) to the future!

SAMUEL SUSSMES CRISPR babies - what now for genome editing?

EMMA MEE-HAYES Fraud-ian slips - misconduct in science and how to prevent it MICHAEL ORRELL Cure-rious about cancer SHAKIRA MAHADEVA Improving therapies with engineering BARBARA SOUZA The disaster memo NOAH HEARNE Nancy Roman, “The mother of Hubble” AMITY ROBERTS

Editorial With current events being as they are, it can be so tempting to view the challenges faced by scientists, and by the world as a whole, as insurmountable.

However, in this issue of the Oxford Scientist, we are focussing on people that have risen to challenging conditions and achieved incredible things.

Be it using the century-old principle of phage therapy to battle antibiotic resistance, fighting cancer using ultrasound and new MOF technologies, or treating PTSD patients with a retro arcade game, the scientific community remains, as ever, home to some of our best causes for hope and optimism in these extraoridinary times.

This term I have decided also to include a few highlights from the University itself, and I have tried to shine a spotlight on the promising work of just a handful of postgraduates who are already tackling major modern issues.

My hope here is to show a more positive picture of where we are and where we are heading - to offset some of the more pervasive, pessimistic attitudes that are hanging over the media this year. I hope to show that the challenges that face us are indeed surmountable, and that we are uniquely privileged to be part of a community whose members are intelligent and resourceful enough to meet them head on.

Olivia Shovlin, Editor-in-Chief

What will it take to feed the world in 2050?

MATT JORDAN

With the need to increase the global food supply becoming increasingly urgent, Matt Jordan explores the limits to which we might realistically push our planet, and what we can do to ease the pressure.

The consequences of anthropogenic environmental change are rapidly moving up the public and political agenda. In particular, the contribution of the global food system to deleterious environmental change is coming under increased scrutiny. This is not without good cause. Marco Springmann, based at the University of Oxford, published a paper in Nature in October 2018 entitled “Options for keeping the food system within environmental limits”. It highlights the extent to which global food production has severe negative environmental impacts. Under a business-as-usual scenario, these impacts are predicted to increase by 50-90% by 2050.

The paper considers so-called ‘planetary boundaries’ which “define the safe operating space for humanity with respect to the Earth system”; in other words, the degree to which we can alter the planet without affecting the regulatory processes that make it habitable for humans. When the planetary boundaries concept was first proposed in 2009, nine processes were identified which underpin them, and three of these - climate change, rate of biodiversity loss and the nitrogen cycle - were considered to have already been ‘overstepped’, or excessively disrupted. Fast-forward to the present, and the global population is expected to grow 23-45% by 2050.

In a hypothetical “business-as-usual”, baseline scenario, this population growth combined with related changes in food consumption would lead to all of the proposed planetary boundaries being crossed by 2050.

Therefore, the challenge we face is not simply to feed 10 billion people by 2050, but to do so without violating these boundaries in an unacceptably harmful way.

Springmann et al. model the potential of three options to reduce the environmental impacts of food production: reducing food loss and waste, promoting technological advances to improve the efficiency of production, and enacting consumption changes towards better, healthier diets. For each, two scenarios are considered: medium- and high-ambition.

Currently, one third of all food produced is wasted - thrown away before it reaches market or as household waste. Cutting food waste by a half would reduce environmental impacts by 6-16%, and a 75% reduction would reduce environmental impacts by 9-24% compared to the baseline prediction for 2050. Technological changes such as increased yield, improved efficiency of nitrogen fertiliser application and improvements in water management would reduce environmental impacts of the food system by 3-30% for medium-ambition, and 11-54% for high-ambition scenarios.

Changing diets in line with guidelines about consumption of red meat, sugar, fruit and veg could reduce greenhouse gas emissions by 29%, whilst movement towards more plant-based (‘flexitarian’) diets could deliver a 56% reduction in food-system emissions.

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Despite the sobering environmental impacts of our food production systems, Springmann et al. provide a hint of optimism by observing that achieving all measures of medium ambition could reduce predicted environmental impacts for 2050 by 25-45%. Combining all high-ambition measures could deliver reductions of 30-60%, equating to impacts that are 20-55% lower than the present.

Whilst these models are thought-provoking, there are two important caveats. First, models are never perfect, and so although the results of this paper are informative, the exact values of the predictions shouldn’t be seized upon too fervently. Indeed, the authors dedicate a section of their paper to uncertainties in the model. Secondly, neither the medium- or high-ambition measures modelled are going to happen automatically; government policies and individual participation will be required to drive the necessary changes across the food supply chain.

Therefore, although this study provides a glimmer of hope, indicating that there are options for feeding the world without catastrophic environmental damage, it will require significant changes in our global food consumption and production; a challenge we all are responsible for meeting.

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NICOLE HASLER

Pore over this Advances in DNA sequencing

Ten years ago, the completion of the Human Genome Project became a milestone in the history of science. The race to be the first team to decode an entire human genome ultimately ended with the two largest groups collaborating and announcing the success of the project in 2001. This was not only a scientific achievement, but also an ideological one. The project spanned 15 years and fuelled an era of technological advancement in DNA sequencing which continues to this day.

One such advance was announced less than a month ago, when a UK research group led by Matt Loose at Nottingham University announced they had sequenced a strand of DNA 10,000 times longer than the usual standard length using a technology known as nanopore sequencing.

The significance of this achievement lies in the continuous sequencing of such a long strand of DNA. Sequencing DNA allows us to decode the information

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stored inside a cell and then better understand how it behaves. Up til now DNA sequencing technology has required the DNA to be chopped up into small sections that are then sequenced and reassembled by a computer to generate a copy of the genome called an assembly. This process is similar to solving a jigsaw puzzle – overlapping ends of the short fragments are compared, and the sequence is assembled by comparing the matching regions. The data can be hard to assemble into a complete sequence, especially in regions that look similar to other parts of the genome or where there are many repeats of a short sequence. This in turn makes it difficult to determine how many repeats are present or which sequence belongs to which region of the genome,leading to gaps in the finished assembly. As such, there is an incentive to develop “long- read� sequencing techniques that allow longer continuous sequences to be decoded.

Nanopore sequencing, developed in 2008, works by using an electric field to

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pull DNA towards a positive charge. In order to reach the positive charge, the DNA has to travel through a narrow pore in a membrane. This pore, has a diameter of just 1.5 nm at its narrowest point, meaning that only single -strands of DNA can pass through.

As the strand goes through the pore, individual bases block the opening. This, causes minute changes in the electrical conductance of the membrane, which can be recorded. As each base has different properties based on its physical structure, a unique profile of duration and magnitude of the pore blockage for each base can be identified, and used to determine the identity of the base. In this way, the sequence of the strand passing through the pore can be identified, with the length of the read depending only on the successful preparation of this fragment. The technique is extremely fast, so that if the entire human genome were encoded in a single DNA fragment, it could be decoded in just 20 hours.

Plus, the cost of sequencing is significantly lower than existing techniques,

NICOLE

as fewer enzymes and nucleotides are needed.

The technique is currently being developed for commercial use by Oxford Nanopore Technologies, which has released several devices for nanopore sequencing. One of these systems, the MinION, consists of a small, disposable sequencing chip that contains the nanopores, required fluidics, and electronic sensors, and is approximately the size of a small cell phone. All that is needed to use it is the prepared DNA fragment and a laptop with a USB port to plug it into. The portability of devices like the MinION is one of the aspects that gives nanopore sequencing such great potential: sequencing can now be done anywhere, without access to a laboratory and the large machines that were previously needed to sequence DNA. This allows the MinION to perform rapid and mobile DNA sequencing with ease.

These advantages have not escaped notice; the MinION has begun to be used to acquire information rapidly in clinically relevant situations both in

remote and urban areas.

The device was used to identify Salmonella strains following an outbreak in a British hospital, identifying the strain far faster than, and just as accurately as, other major sequencing techniques. Perhaps most excitingly

though, the MinION allows sequencing to occur in areas where little laboratory infrastructure is available by, eliminating the need for expensive and bulky equipment. In the recent West African Ebola epidemic, researchers used the devices to sequence the viral genomes from 14 patients within only 12 days.

The viral genomes can

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HASLER

then be used to track the evolution and spread of the virus and, importantly, to diagnose Ebola and other endemic diseases, such as Chikungunya Virus or Hepatitis C. The record-setting DNA read recently obtained by the Nottingham group is part of the trend towards faster, cheaper long-read sequencing technologies.

These developments will aid the identification of pathogens, diagnosis of infections, and enable tracking of disease outbreaks in real-time. It’s not all about saving lives though. Scientists are a competitive bunch and a big driver of these innovations is the friendly competition that occurs between research groups. This is embodied by the recent creation of a trophy that is allocated to the group that holdsthe record for the longest read. For now, the trophy sits in pride of place in Nottingham and there it will remain until the next advance in long-read sequencing whisks it away.

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CAITLIN ASHCROFT

WHO DO YOU I THINK YOU ARE? The science of first impressions How long does it take to warm to someone you’ve just met?

Or to win over a potential employer during an interview?

The answer, it seems, is less than the blink of an eye.

Within an instant of meeting, often without uttering a single word, we are programmed to draw inferences about a person’s character based solely on the evidence of our eyes. Indeed, there is evidence to suggest it takes as little as 1/10th of a second to generate a first impression of a stranger’s face. While we may think that our opinions of the people around us are built upon careful observations of their behaviour, personality, and values; the rapidity, power and enduring nature of first impressions suggests our social reasoning may rely on something entirely different.

So what’s really going on?

In the 1950s, Herbert Simon coined the term ‘bounded rationality’ – a model of human reasoning based on the assumption that our decision-making processes are subject to unavoidable cognitive limitations.

Although we may consciously strive to make rational decisions, our limited capacity to process information prevents us from always being able to consider all aspects of a problem. We simply don’t have the time or the mental resources to perform an in depth cost-benefit analysis every time we choose our breakfast in the morning. In order to compensate for these limitations, we

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tend to rely on a number of mental shortcuts to ‘fill in the gaps’ in our decision-making processes and improve our ability to make quick and efficient judgements.

In social psychology, these are known as heuristics: automatic, easily implemented mental ‘rules’ that allow us to focus on the salient aspects of a complex problem while ignoring irrelevant information.

Nobel Laureate Daniel Kahneman, and his late colleague Amon Tversky, made their mark this field by demonstrating the existence of several key heuristics that underlie a wide range of our intuitive judgments. For instance, whether we are consciously aware of it or not, we typically generate better first impressions of people who look similar to us - an example of the ‘similarity heuristic’. While this may sound like the height of vanity, it’s easy to see the potential benefit. People that look like us are more likely to come from similar backgrounds, and therefore to share our values, beliefs and experiences. As such, they’re probably safer bets when it comes to making friends. Similarly, people with traits often associated with specific stereotypes typically causes us to generalise other aspects of that stereotype to them; a well-dressed man is likely to be perceived as smart and poised, while someone dressed in worn jeans and a ripped shirt is more likely to be seen as unprofessional and unreliable (the ‘representativeness heuristic’).

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Heuristics can be very helpful in day to life and are often reasonably accurate - stereotypes exist for a reason, after all - but they can also lead us astray. One of the major dangers of reliance on heuristics when making decisions is that they typically exploit our pre-existing biases and prejudices. A prime example of this may be observed in the world of professional musicians. Women have historically been vastly underrepresented in orchestras. In fact, before the 1970s, the proportion of women in the top five US orchestras was just 5%. However, when orchestras began conducting blind auditions – where the identity of the auditionee remains a mystery throughout – as a means of avoiding implicit gender bias, the number of women increased dramatically.

This highlights two important points about the processes underlying our social judgements.

First, that our expectations, past experiences and beliefs will inevitably shape the way we react to the people we meet. And, second, that it is only through being aware of this that we can hope to combat the engrained often unconscious - prejudices they give rise to. As such, while eliminating the implicit bias in our first impressions is far easier said than done, we nonetheless have a responsibility to limit the extent to which they dictate our behaviour.

HARRIET HARDY

Scientists develop a universal cancer blood test that can detect any kind of cancer within 10 minutes Researchers at the University of Queensland, Australia have developed a blood test that can detect whether or not a patient has any type of cancer within as little as 10 minutes. Although still in the initial stages of testing, this cheap and simple method could help clinicians to diagnose cancer before symptoms appear, when the widest range of treatment options are available.

Cancer diagnosis relies on the ability of patients and clinicians to spot the signs and symptoms of disease, which often go unnoticed until the cancer has progressed. Screening programmes increase the chances of early detection but the currently available screening tests are expensive, time-consuming and are specific to individual types of cancer.

The new method, published this week in Nature Communications, claims to be able to detect the presence of cancer cells anywhere in the body using a simple and non-invasive blood test. This universal cancer test hinges on a key difference in the DNA of healthy and cancerous cells, which affects how well it binds to metals such as gold.

This is a property that can be measured using a simple colour changing test.

Cells regulate when and where genes are switched on and off through a DNA chemical modification known as methylation.

In healthy cells, DNA is heavily decorated with methyl groups which are spread out across the genome. In cancer cells, most of

the methyl groups are removed, leaving only small clusters of methylation. The authors refer to this unique cancer methylation pattern as the ‘Methylscape’.

Professor Matt Trau, who led the research, said, “It seems to be a general feature for all cancer. It’s a startling discovery.”

Co-author Dr. Abu Sina added, “Because cancer is an extremely complicated and variable disease, it has been difficult to find a simple signature common to all cancers, yet distinct from healthy cells.”

The researchers found that the ‘Methylscape’ of cancer DNA affects its chemical properties.

When DNA is added to water, the methyl groups cause the DNA to fold up into nanostructures. Due to the lower numbers of methyl groups, tumour DNA forms fewer of these nanostructures than healthy DNA. This means that it has a larger surface area, which allows it to bind much stronger to metals such as gold than the bundled up, healthy DNA. How strongly DNA binds to the surface of gold can be measured electrochemically or with a colour changing test, visible to the naked eye.

The method was tested on over 100 blood samples from patients diagnosed with breast or colorectal cancer, and 45 samples from healthy individuals and was able to reliably distinguish between healthy and cancerous DNA. The authors are hopeful that their method could, therefore, be used as a non-invasive screening test that is sensitive CHALLENGES

enough to detect the low levels of tumour DNA which circulate in patient blood. Such a test could provide a simple yes or no answer as to whether a patient has cancer. The location and stage of disease would then need to be determined with further tests.

Whilst the study has caused a lot of hype in the media over the last few days, the method is still in the initial stages of testing and it will be some time before it could be ready for clinical use.

“We certainly don’t know yet whether it’s the Holy Grail or not for all cancer diagnostics,” says Trau, “but it looks really interesting as an incredibly simple universal marker of cancer, and as a very accessible and inexpensive technology that does not require complicated lab-based equipment like DNA sequencing.”

It is also important to note that the samples used in this research were from patients diagnosed with advanced stage cancer. The method will need to prove its sensitivity to detect the ‘Methylscape’ signature in patients with earlier stage disease, who likely have lower levels of circulating tumour DNA. Ged Brady, of the Cancer Research UK Manchester Institute, said, “This approach represents an exciting step forward in detecting tumour DNA in blood samples and opens up the possibility of a generalised bloodbased test to detect cancer. Further clinical studies are required to evaluate the full clinic potential of the method.”

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PRATIBHA RAI

Tetris in the Lab: The Surprising Link Between PTSD and Tetris In December 2018, a notable study was published in the Journal of Consulting and Clinical Psychology; “Reducing intrusive memories of trauma using a visuospatial interference intervention with inpatients with posttraumatic stress disorder (PTSD)”. Post-Traumatic Stress Disorder impacts people who have experienced extreme traumatic events such as war or torture. PTSD sufferers are vulnerable to disturbing, involuntary memories of traumatic events (colloquially called ‘flashb a c k s’ ) , which are a debilitating symptom of the condition.

This recent study suggests a lenitive method to treat PTSD flashbacks through ‘a visuospatial interference intervention’. The procedure however, is unconventional, as the study believes that playing the computer game Tetris could alleviate patients’ flashback frequency.

Invented in 1980s Moscow, Tetris is a classic tile-match-

“Tetris is a game with high levels of visuospatial demands, thus it disrupts the sensory elements of the trauma memory” 10

ing puzzle game, which involves slotting various shapes of ‘Tetriminos’, by moving them sideways and/or rotating pieces by quarter-turns, in such a way that they form a horizontal line. When a line is formed, it disappears and yet more Tetriminos fall at an increasing speed. The game ends when there is no more space to stack Tetriminos. The unusual link between PTSD and Tetris might leave some incredulous, but it is a link that has been proven repeatedly in laboratory and clinical experiments.

The most recent study cited above was led by Dr Aram Kehyayan and Professor Henrik Kessler from the LWL University Hospital Bochum, together with Oxford Visiting Professor Emily Holmes who is now based at the Karolinska Institutet.

Their study involved 20 inpatients with complex PTSD who received regular therapy for six to eight weeks.

They wrote a stressful memory down on paper, which they then tore up, without discussing the memory, and followed this by playing Tetris for 25 minutes on a tablet. The team found that the frequency of flashbacks decreased as days, even weeks progressed. Over the weeks, other stressful events were targeted and each time, the number of inHILARY 2019

voluntary visual memories dwindled. To quantify their result, the behavioural intervention procedure using

Tetris evidenced that flashbacks fell by around 64%; an astonishing difference when one considers the impact this may have to PTSD sufferers.

Why does Tetris work alongside PTSD? Researchers believe that it is because the areas in the brain responsible for visuospatial processing are activated when patients visualise a stressful memory and these are the same areas of the brain, which are hypothetically used when playing Tetris, thus causing interference. Tetris is a game with high levels of visuospatial demands, thus it disrupts the sensory elements of the trauma memory. Might it be the brain’s competing for comparable and limited resources involved in each task that prov ides the link?

Though the study was published last year, it has extended from earlier re s e a rc h

conducted by Professor Emily Holmes, who studied psychology at the University of Oxford. Her awareness of the connectivity between PTSD flashbacks and the palliative powers of Tetris was discovered in 2009. She had led an experiment whereby 40 healthy volunteers were shown traumatic material, and after 30 minutes, half of them played Tetris and the others did not. The results evidenced that the volunteers who played Tetris had substantially fewer flashbacks than their peers.

This so-called ‘dampening’ of flashbacks was suggested to be due to Tetris competing for sensory resources in the brain. The following year, her team suggested a ‘cognitive vaccine’ against PTSD flashbacks, which involved playing Tetris after exposure to trauma.

2017 saw Professor Holmes and her colleague at Oxford, Dr Lali Iyadurai, carry out a clinical experiment, involving real patients who had undergone a traumatic vehicle accident to test their hypothesis. The move from experimental trauma in controlled environments to real-world trauma would be a litmus test as to the credibility of the PTSD-Tetris theory. Their hypothesis was that patients who received the behavioural intervention of playing Tetris while waiting in the Emergency Department would experience fewer intrusive memories of the event. The study included 71 vehicle accident victims; half of them recalled the trauma followed by playing Tetris while they waited in the hospital, and

the control group performed another task. The findings of the experiment was a success – those who played Tetris had fewer traumatic memories in total during the week immediately after the accident than the control group.

Whether one finds the research challenging or encouraging, it is true to say it is certainly timely in the field of PTSD research. Flashbacks are a crippling feature of PTSD and thus should be a significant target for intervention. Where therapies are available, places are limited, as trauma therapist and senior physician, Henrik Kessler, notes, “there are many more patients than therapy places. That’s why the researchers are looking for methods outside conventional treatments that can relieve the symptoms.” If the Tetris technique can be trusted, as they have shown themselves repeatedly to be, then it would provide a non-invasive way to manage the malady.

It would also be a non-pharmacological option, an ever-relevant issue as there has been recent controversy over certain drugs such as propranolol to ‘eradicate’ post-traumatic flashbacks memories. Similar to the protein-synthesis inhibitor anisomycin, which weakens fear memory for animals, the beta-blocker propranolol reduces physiological responses to fear cues in humans. However, such pharmacological inter-

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ventions could potentially be deleterious as post-trauma memory recall is important for instance, in legal procedures. The current data suggests that Tetris game-play only dampens flashbacks, while knowledge of the traumatic event remain unscuppered. As Professor Holmes’s team believes, rather than ‘e r a s i n g ’

traumatic memories or cognitively ‘suppressing’ unwanted memories, it is still important for individuals to have the ability to choose to recall the event.

PTSD is an important realm of research that, similar to many mental health conditions, deserves more scientific understanding and public awareness. A decade after Professor Holmes brought our attention to the phenomenal, if bizarre, relation between PTSD and Tetris, we are still at the beginning of this innovative research. As Holmes has stated, it would make a great difference to many people if we created “behavioural psychological interventions…to prevent post-traumatic suffering and spare them these grueling intrusive memories. This is early days and more research is needed.”

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JONATHAN VINCE

Using ultrasound to improve cancer treatment 1st year PhD student Jonathan Vince has been awarded an industrial fellowship by the Royal Commission of 1851 on improving a crucial treatment for hepatic cancer.

Diagnoses of liver cancer are at unprecedented ments of individual patients. Therapeutic suclevels and growing at an alarming rate, partic- cess is determined by the density of irradiation ularly in sub-Saharan Africa and Eastern Asia, facilitating tissue death. With a variety of prodwhere the co-occurrence of other debilitating ucts available of varying isotopes and dosages; diseases such as liver cirrhosis, Hepatitis B or there remains one final hurdle to overcome in C, obesity, diabetes and non-alcoholic fatty liver improving and diversifying the potential of SIRT escalate the complexity of the disease. Currently and that is the distribution of the beads within liver transplantation remains the ‘gold standard’ the tumour. of treatment, however for patients not eligible The delivery of the beads into the arterial vasfor transplant, there is a limited number of treat- culature and the proximity to the cancerous lements available for smaller lesions in the early sion(s), is currently solely dependent upon the stages of the disease; including resection, che- physician’s ability to predict and respond to the motherapy and various ablation therapies. Selec- changes of flow within the individual’s vascutive internal radiation therapy (SIRT), although lature. There is currently no method by which not as common place as external beam radio- the beads’ positions can be controlled within the therapy or chemotherapy, is becoming a life-line patient after the initial delivery. My current refor cancer patients who previously would have search aims to address this challenge by using ulhad very limited options. trasound to non-invasively distribute the beads, SIRT uses micro-embolic radioactive micro- thus providing physicians with a concurrent or sphere ‘beads’ which are delivered via a mini- follow-up procedure to allow re-distribution mally invasive microcatheter. The microspheres and movement of the radioembolic particles contain a transition metal covalently bound within the body; further improving selectivity within the microspheres. The transition metal contained in the microspheres is carefully “Selective internal radiation therachosen, so that once exposed to particle bom- py (SIRT), although not as common bardment, only a single radioactive isotope is produced. Using a single isotope rather than a place as external beam radiotherapy combination of radioactive elements produces or chemotherapy, is becoming a lifea therapy with predictable release energies and line for cancer patients who previtime frames from a single emission spectrum, ously would have had very limited for accurate calculation and radiation dosing. options.”

This significantly reduces the radiation dose in healthy tissue, thus reducing harmful side effects and increasing the chances of reducing the tu- and hopefully patient outcome. mour size so that it may become eligible for surThis work is funded by the Royal Commission gical removal. of 1851, with support of BTG and the Institute of Radioembolic beads can vary in mechanical, Biomedical Engineering, Oxford University. chemical and radiation emissions; offering the ability to tune the SIRT treatment to the require-

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HILARY 2019

DR MARTINE ABBOUD

Spotlight - Dr Martine Abboud Dr Martine Abboud is a multi-award winning scientist. She works in the Schofield group in the Department of Chemistry and is a Junior Research Fellow at Kellogg College. Martine writes to ‘the Oxford Scientist’ about what she does and her passion for research.

During my time in Oxford I have discovered a genuine interest for scientific research which has been undoubtedly enhanced by the international culture of our laboratory. The interdisciplinary nature of my work and its collaborative aspects keep me motivated. I enjoy being in the lab, talking to people, and doing ‘fun’ science that matters!

As a first-generation graduate, I believe that science has no nationality, Oxford is accessible, and research has no boundaries. Accordingly, I have been involved in fostering diversity in the chemical environment by sitting on various consultative and executive committees, acting as a student advisor, and delivering engaging outreach talks at state schools. I have also been engaging the public with research via active science communication and event organisations, including tech-based lectures in under-developed countries to raise awareness about global health issues, including antibiotic misuse.

My research at the interface of biology, chemistry and biophysics has led to novel method development and advances in three different areas of scientific research.

These include oxygen sensing, antibiotic resistance, and metabolic alterations involved in cancer (see below).

How do we sense oxygen?

At high altitude, the atmospheric pressure is lower, so you breathe in less oxygen. Cells in our bodies have sensors that detect lower oxygen levels and have developed mechanisms to adapt to them. Over time, they boost their blood supply in order to compensate for the lower oxygen levels. This natural response is important in various diseases and hence, its manipulation is desired in certain conditions. For example, drugs that boost the delivery of oxygen are of interest in the case of anaemia and cardiovascular diseases while turning off oxygen delivery is advantageous in tumours. My work has fo-

cused on the human prolyl hydroxylase domain-containing protein 2 (PHD2), which is crucially involved in the body’s response to oxygen. Our work showed that the substitution of a single amino acid, as occurs with PHD2 variants linked to erythrocytosis and breast cancer, can alter the selectivity of PHD2 towards its substrates. Comparative studies on the activities and selectivities of PHD inhibitors in clinical trials have helped us understand the oxygen sensing response and informed on new drug development.

What is antibiotic resistance?

Antibiotic resistance is an immediate and growing global health threat. It is estimated that within the UK 8.2 % of hospitalized patients contract a hospital-acquired infection costing the National Health Service >£1 billion per annum. β-Lactams (e.g. penicillins, cephalosporins, and carbapenems) remain the most important class of antibiotics, representing 60% of all antibiotics used; however, their use is threatened by antimicrobial resistance. My work focused on metallo-β-lactamases (MBLs), which are bacterial enzymes that degrade the β-lactam antibiotics. Method development work has provided new structural insights into MBL catalysis and has stimulated novel inhibitor development. I also studied the susceptibility of avibactam, the first clinically useful non-β-lactam β-lactamase inhibitor, to MBL-catalysed hydrolysis. The use of ligand-observe NMR as a screening method coupled with virtual screening has led to the identification of the first non-metal chelator MBL inhibitors. My work has also enabled better understanding of the MBL mechanism.

How does altered metabolism induce tumorigenesis?

More recently, I have become interested in how altered metabolism promotes cancer. Although pioneering attempts are being made to target mutant forms of isocitrate dehydrogenase (IDH) for the treatment of leukaemia and brain cancer, these are hampered by a lack of understanding of the metabolic and biochemical consequences of the mutations. Understanding those might lead to therapeutic benefits for patients with cancer, potentially in a prophylactic manner.

For this article’s bibliography, visit oxsci.org.

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NOAH HEARNE

Worst Journey, Winter Journey Edward Adrian Wilson could be called a doctor or an artist, but primarily he was a naturalist. The man was known by his colleagues to possess immense talent and impeccable character. Since first travelling to the Antarctic on the Discovery expedition, Wilson believed that one of Antartica’s more famous inhabitants, the emperor penguin, was the most primitive of all birds, linking them to their reptilian cousins. He hoped on a second journey to Antartica, Terra Nova, he could collect a series of eggs housing embryos of varying degrees of development, ‘[showing] remains of the development of an animal in former ages and former states; it recapitulates its former lives’.

Wilson took two men, Apsley Cherry-Garrard and Henry ‘Birdie’ Bowers, and set off from a base at Hut Point on Ross Island off continental Antartica to Cape Crozier, the only known site of an emperor penguin rookery, on a 67 mile, month-long trek. The men hiked for weeks, facing the brutal force of the Antarctic: perpetual night, fog, frost-bite, lows down to -80°F, frozen breath, sweat, and sleeping bags, hitting ‘bed-rock’, as Wilson put it, with 48 hours of building an igloo of rock and ice.

Reaching the orphan rookery took climbing through a hole in a towering ice wall and racing against the fleeting light of the ephemeral day. The men, ‘three crys-

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tallised ragamuffins, above the Emperors’ home…’, found the birds and collected the only eggs they could find, a total of five, all empty. On the return journey, storms tore apart the men’s igloo, faces froze, crevasses opened below tired feet, and two of the penguins’ eggs turned to dust.

With their arrival and the safety that Hut Point’s small shack provided, Wilson said, ’I want to thank you two for what you have done. I couldn’t have found two better companions – and what is more I never shall.’

Wilson and Bowers next set off with Scott and two others to the South Pole. A black flag at their destination told the men ‘the worst has happened, or nearly the worst’, Scott wrote; a competing Norwegian expedition had beat them to it. With that, the only direction left to head was North, back to their base and then onto home. This return trip was less forgiving than Wilson’s trek to and back from the rookery, which Cherry-Garrard described as ‘the worst journey in the world’; however, facing that indifferent force of the Antarctic, this polar party of the Terra Nova expedition fell victim to the cold and ‘[met] death with as great a fortitude as ever in the past’.

HILARY 2019

Challenges on every scale:

MARIA VIOLARIS

the mini-project microcosm of Hofstadter’s butterfly.

How serendipity surpassed challenges in a fractal fusion of maths and physics.

On the fourth day of my third year mini-project, I was once more slowly turning a dial. It was easy to forget that I was cooling down a state-of-the-art semiconductor sample to just above absolute zero (0.6K) using potentially explosive liquid helium, investigating open questions about the quantum hall effect, as I produced graph after graph that disagreed with the lab script. My challenge was one frequently faced by many Oxford physicists: working out what has gone wrong in the undergraduate lab.

Writing up my report over the Christmas vacation, I searched ‘the quantum hall effect’ on Wikipedia to glean some contextual insights. I scrolled past the normal explanation, that electrons jump from one energy level to another as the magnetic field increases, due to the increased Lorentz force. Then a beautiful, unfamiliar picture emerged, captioned ‘Hofstadter’s Butterfly’.

It turned out that behind this picture, Douglas Hofstadter had his own set of challenges.

He began as a number theorist – but when he went to graduate school, was disheartened by the abstract departure from integers and abandoned mathematics. He entered particle physics, believing it was the only exciting area of physics of the time (1970s); then after passing through a chain of PhD advisors was prompted by the overwhelming zoo of new particles to quit. He found a supervisor, Gregory Wannier, in solid state – an area of physics he originally viewed with disdain – working on a project to understand how electrons behave in a 2D solid in a magnetic field. Strangely, the properties of the electrons depended on rational and irrational numbers… precisely the mathematics Hofstadter loved investigating as an enthusiastic student of number theory in his youth.

Applying this unique background, Hofstadter discovered that 2D electrons in a magnetic field are described by ‘Hofstadter’s Butterfly’.

This fractal pattern is composed of infinitely many smaller, distorted versions of itself.

Wannier was unimpressed, disbelieving the fractal claim. He suggested Hofstadter do a library thesis (just collect other peoples’ ideas) because he would do no original work. “Put

numerology in the appendix.*” However, Hofstadter persisted and coincidentally stumbled upon a spare computer with a plotter to produce an even more detailed ‘butterfly’ – finally convincing a shocked Wannier that this really did emerge from electron behaviour.

Hofstadter used the butterfly to obtain his PhD and leave physics on a success, believing he had stumbled on a one-off discovery through a serendipitously relevant background. He returned to his beloved manuscript of GEB (Gödel, Escher, Bach), which he had locked away to force himself to work on his PhD. Hofstadter never expected the fundamental legacy ‘Hofstadter’s butterfly’ imprinted on condensed matter research, including the explanation of the quantum hall effect. The different sized butterfly wings correspond to consecutive integers, labelling the energy levels that electrons can occupy subject to different applied magnetic fields.

The butterfly has only been verified by recent experiments – using similar technology to my mini-project. This tenuous link between my challenges and Hofstadter’s almost seemed to parallel ‘Hofstadter’s butterfly’ itself with distorted self-similarly. Challenges repeat themselves in physics on every scale: at each moment of our experiment we face a practical challenge; the overall experiment is facing the challenge of explaining the unknown physics; and this is just one challenge in the context of many challenges faced by physicists like Hofstadter to describe the fundamental theory in the first place.

My next challenge: somehow embed Hofstadter’s mesmerising butterfly into my mini-project report. Maybe that will detract attention

CHALLENGES

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Why is chaos so chaotic?

Since Galileo’s times, we equated determinism with predictability. With Newton’s laws of motion, Laplace hopefully claimed “If we were to know with precision the positions and speeds of all the particles in the universe then we could predict the future with certainty”. Physics and its mathematical models promised us long-term prediction of a system’s behavior in theory. We think that all future events are uniquely determined by initial conditions. We think that the world is a predictable mechanical system, a clockwork universe. But thanks to chaos, in practice we will only be able to do so if we have an infinite degree of measurement and computational accuracy.

Chaotic systems themselves do not look chaotic. They are deterministic, nonlinear dynamical systems. That is how simple mechanical systems which we feel we should understand outsmart us. We understand the double pendulum – we know the Lagrangian for it based on Newton’s laws of motion, and the solutions for the equations that tells us what its motion should be. To our dismay, there is no discernible regularity or order to be found in our observations. Despite we can compute the motion of the pendulum, we cannot predict how the pendulum moves a short time after we release it. Even computers predict that a double pendulum should move in an essentially random and unpredictable fashion.

In the 60s, meteorologists began experimenting with statistical forecasting. Computer simulations of basic weather patterns were governed by a set of differential equations from fluid mechanics, started off by observational atmospheric data as initial values. American mathematician Edward Lorenz found periodic patterns or precisely repeating sequences in his simulations. While these are mathematically true modelling results, we all know weather never works that way – it is too regular to be realistic. Rounding off one variable from .506127 to .506 in his repeated simulation, he changed the whole pattern produced by the program drastically. This implies errors in observing small-scale weather features or the slightest rounding errors in numerical computation could evolve into large-scale errors in a day. Lorenz had an epiphany – Our failure in forecasting nonperiodic behavior is not a matter of mathematical misdescription. It is the sensitivity of our well-understood and well-solved equations to initial conditions. No set of data is perfect, nor are computers perfect at solving the equations. Unpredictability is inevitable.

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Before the discovery of sensitive dependence in dynamical systems, Aristotle found a counterpart in methodology and epistemology - “the least initial deviation from the truth is multiplied later a thousandfold”. Similarly, the least initial deviation from input of a set of deterministic equation is multiplied later a thousandfold, emerging as unpredictability. The butterfly effect poetic reiteration of this phenomenon – tiny air currents of a butterfly’s wings flapping can amplify to cause a hurricane on the other end of the world. In 1987, the term “butterfly effect” took flight in James Gleick’s best seller Chaos: Making a New Science—and Lorenz’s discovery reached a general audience. Butterfly effect came into our public consciousness, inspiring songs such as Butterfly Effect

by Travis Scott and Butterflies and Hurricanes by Muse, and movies such as The Butterfly Effect series.

A less poetic illustration of this phenomenon is through the Lyapunov exponent. Given two infinitesimally close starting trajectories in the phase space, with initial separation Z0 , the two trajectories end up diverging at a rate given

by Zt≈eλt|δZ0|, where t is the time and λ is the Lyapunov exponent. In other words, each point in a chaotic system is arbitrarily closely approximated by other points with significantly different trajectories. An arbitrarily small perturbation of the current trajectory would lead to exponentially growing divergence in future behavior. The orientation of the initial separation vector determines the rate of separation, i.e. the sensitivity to initial conditions. While a whole spectrum of Lyapunov exponents exist, the maximal Lyapunov exponent is most often used because it determines the overall predictability of the system. A common mathematical description of chaos found in physics literature is: A system is chaotic if it has a positive maximal Lyapunov exponent.

The three factors that determine how long we can effectively predict a chaotic system are: how much uncertainty can be tolerated, how accurately the current state can be measured, and the Lyapunov time. The Lyapunov time measures how long it takes for two almost-identical states of a chaotic system to exponentially diverge. The horizon of predictability is set by the Lyapunov time– typically an interval of within two or three times the Lyapunov time. The shorter the Lyapunov time, the more rapidly similar states depart for disparate futures, the more sensitive the system is to initial conditions.

For example, the Lyapunov time of chaotic electrical circuits is around 1 millisecond; that of weather systems is a few days,

HILARY 2019

ARLENE LO

while that of the inner solar system is 4 to 5 million years.

With exponentially growing uncertainty in forecast, it is a fate that meaningful predictions become impossible to make in the end.

Last year, physicists employed reservoir computing to formulate a method for model-free estimation from data of the Lyapunov exponents of a chaotic process. They chose the Kuramoto-Sivashinsky equation, a model for diffusive instabilities in a laminar flame front, as their testing ground to study turbulence and spatiotemporal chaos. The challenges of the Kuramoto-Sivashinsky equation are the high dimensional nature of the system and large number of Lyapunov exponents. Their reservoir computing approach managed to closely predict the evolution of the flamelike system out to eight Lyapunov times – eight times better than previous methods! To achieve the same advancement, we would need to have measured the initial conditions 100,000,000 times more accurately.

The “reservoir” of reservoir computing is a high-dimensional dynamical system with a limited time series of measurements as input. Data-streams are fed into randomly chosen artificial neurons in the reservoir. With the recorded neuron responses to the data, output weights (a large set of parameters) are learnt through linear regression. The learned output weights are used to build a modified autonomous reservoir. If successful, the autonomous reservoir can produce an arbitrarily long time series whose ergodic properties approximate those of the input signal. Knowing the reservoir equations and output weights, we are ready to compute the necessary derivatives to determine the Lyapunov exponents of the autonomous reservoir. The derivatives later used as estimates of the Lyapunov exponents for the original input generating system. This is how a neural network learn the dynamics of the evolving flame front purely from data.

Locality of interactions in spatially extended chaotic systems allows us to use one reservoir of neurons to learn about one patch of a system, and another to learn about the next patch. Interactions are accounted for with slight overlaps of neighbouring domains. Parallelization of the problem enables this approach to handle chaotic systems of any size, given the proportionate computing power is dedicated. As the Kuramoto-Sivashinsky equation also applies for plasma waves and air turbulence,

reservoir computing can help us predict rogue waves and even earthquakes. A particularly important application is giving advance warning of solar storms, where the magnetic outburst would severely damage Earth’s electronic infrastructure.

Machine learning opens up a more likely avenue for improving weather forecasting and similar prediction efforts.

The reservoir computer has no clue of the Kuramoto-Sivashinsky equation. It only sees data recorded about the evolving solution to the equation. We do not need to have complete ultra-high-resolution data or perfect physical models in order to unravel chaotic phenomenon. Deep learning, while being more complicated and computationally intensive, and other machine-learning algorithms are postulated to work well for tackling chaos. Why machine learning performs surprisingly well at learning the dynamics of chaotic systems is unclear. Yet, chaos theory lends researchers a new perspective in understanding the internal machinations of neural networks. Like fractals in computer graphics generation and chaotic signals in modern encryption systems, chaos proved itself useful in unpredicted ways again.

Acclaimed to be on par with relativity and quantum mechanics as the great scientific revolutions of the 20th century, chaos theory brings us both good and bad news.

The good news is seemingly complicated behavior may have mathematically elegant and simple underlying explanations. There is a hope to understand complicated systems, such as stock markets, population of species, erosion of a riverbed and disease epidemics, in terms of simple deterministic rules. The bad news is it proves to us there is a limit to how well we can predict and control the physical world. Even with recent breakthroughs using reservoir computing, chaos will ultimately prevail at sufficiently long time scales. While chaos itself does not invalidate determinism, the apparent randomness only produces an epistemic form of nondeterminism. Predicting the future with certainty is after all a dream.

CHALLENGES

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SCHOOLS COMPETITION We are pleased to announce the results of our Hilary Term 2019 school science writing competition. We received 212 entries from school students across the UK in Years 10-13.

The topic of the competition was “one way in which science impacts your everyday life”. The winning article, selected by our panel of judges, was The Science of a Chilli by Arushika Aggarwal, Year 12, The Tiffin Girls’ School, Surrey. Arushika will receive four tickets to the IMAX 3D experience at the London Science Museum. Eight runner-up articles were also selected by our judges, and will be published alongside the winning article on our website www.oxsci.org .

RUNNERS-UP YEAR 13 RUNNER-UP The Genetic Lottery: Sicle Cell Anaemia and Me, by Tamilore Awosile, The Haberdashers’ Aske’s Boys’ School, Hertfordshire.

YEAR 12 RUNNER-UP The Point of Pencils?, by Ashley Kabue, Year 12, Bablake School, West Midlands.

YEAR 12 RUNNER-UP How Science Impacts My Everyday Life: Mirrors by Sophia Leipnitz, Year 12, Nonsuch High School for Girls, Surrey.

YEAR 12 RUNNER-UP A Toast to the Maillard Reaction by Clarissa Pereira, Year 12, The Tiffin Girls’ School, Middlesex.

JUDGES DR JONATHAN GREEN is a lecturer and researcher in the University of Oxford’s Zoology Department. He is interested in the social lives of animals, specifically what they know about each other and how this information is used to make decisions during social interactions. To answer these questions, he studies a range of animals, including birds, fish and flies.

Dr ELISA GRANATO is a Microbiologist in the Oxford Departments of Zoology and Biochemistry.

She is excited about finding out how tiny microorganisms live their lives, and spends most of her day staring into the microscope to watch glowin-the-dark bacteria do their thing. At the moment, she is trying to work out how gut bacteria use toxic chemicals to kill off their competitors. She is also passionate about science communication, and you can get in touch with her on Twitter (@Prokaryota) JACQUELINE GILL is a DPhil student in Evolutionary Microbiology in the Department of Zoology, University of Oxford. She was a cofounder of The Oxford Scientist magazine, and established the first national Oxford Scientist school science writing competition, and has managed all aspects of the competition since its launch.

YEAR 11 RUNNER-UP Google Maps and the Atomic Clock by Emily Donald, Year 11, Sir Henry Floyd Grammar School, Buckinghamshire.

YEAR 11 RUNNER-UP How Science is Involved Even in the Most Basic Products of Everyday Life by Diyaco Shwany, Year 11, King Ecgbert School, Sheffield.

YEAR 11 RUNNER-UP Tic Tock, When Will it Stop? by Amrutha Vudathu, Year 11, Michaela Community School, Brent.

YEAR 11 RUNNER-UP Thanks a Million, Or Even a Trillion… For Being Theret, by by Haeun Kim, Year 10, Nonsuch High School for Girls, Surrey.

Interested in being the next winner of our Schools Writing Competition?

Pease email competition@oxsci.org for more information.

If your school, sixth form or college would like to subscribe to The Oxford Scientist for just £15 a year, please contact editor@oxsci.org.

ARUSHIKA AGGARWAL, YEAR 12, THE TIFFIN GIRLS’ SCHOOL, SURREY.

SCHOOLS COMPETITION WINNER

The science of a chilli Being born and brought up in an Indian household, chillies have always been an essential ingredient in our daily meals. It just so happens that the chilli pepper has a fascinating evolution behind it, and the way it reacts with our bodies to allow us to experience a unique hot and burning sensation is unparalleled.

Responsible for the heat of chillies is a family of compounds called the capsaicinoids, with the dominant compound being capsaicin, a vanilloid.

The spiciness is a defence mechanism that some peppers develop in order to suppress a microbial fungus caused by insects. Without this protection, the fungus would destroy the plant’s seeds before they can be consumed by birds and widely distributed. The TRPV1 receptor, responsible for the sensation of scalding heat and pain in mammals, is insensitive to capsaicin in birds, therefore birds are able to eat the seeds with no pain. Unlike other plants, chilli peppers increase their chemical defence levels as they ripen, and become spicier, and they are able to do this since birds are unaffected by capsaicin, making chillies in possession of a remarkable defence mechanism.

Spiciness isn’t a flavour- it is simply the result of the activation of pain receptors in the body. When ingested, the capsaicinoids found in chillies bind to a receptor (TRPV1) in the mucous membranes of the mouth, which is stimulated with heat and physical abrasion.

When TRPV1 is activated, it permits cations to pass through the cell mem-

brane and into the cell. The resulting depolarisation of the neuron causes a signal to be sent to the brain through a series of electrical impulses, and hence, a burning sensation is produced. These signals to the brain give a ‘false’ sense of overheating, therefore the hypothalamus, the thermoregulation centre of the body, activates millions of sweat glands to start producing sweat following capsaicin ingestion. Sweat is released from the glands, and is evaporated, thereby cooling down our body.

have an impact.

To relieve the burning sensation, milk is a more suitable option, since milk contains a class of proteins called casein, which is lipophilic and envelopes the fatty capsaicin molecules, successfully washing them away and preventing them from further stimulating the receptors in the mucous membranes.

So despite this, why is it we cannot resist the fiery blast on our tongue? The pain produced causes the brain to respond by releasing another neurotransmitter known as endorphins, which are the body’s natural way of relieving pain by blocking the nerve’s ability to transmit pain signals. Additionally, the neurotransmitter dopamine, responsible for the sense of reward and pleasure, is also released. In essence, this is why eating spicy food can create a euphoria similar to ‘runner’s high,’ and imparts a sense of ‘well-being’ in the body. Furthermore, if capsaicin is ingested repeatedly, the depletion of the receptors can effectively allow you to build up a tolerance, thus making spicy foods easier to eat.

One way in which the heat of chillies can be tested is the Scoville scale. It is a taste test in which a measured extract of the dried pepper is incrementally diluted with a solution of sugar and water, until the heat is no longer detectable.

This method is far from precise, hence the other method is the rather more precise procedure of high performance liquid chromatography (HPLC). In this variety of chromatography, a solvent sample is forced through a column under high pressure, to achieve separation of the mixture.

However, for those who do not enjoy the fire of chillies, why are we told to reach for a glass of milk, rather than water? The long hydrocarbon tail of the capsaicin molecule makes it insoluble in water, however, readily soluble in alcohol and oil. Unfortunately, the small percentage of alcohol in most alcoholic drinks is not substantial enough to

CHALLENGES

Chillies are an essential part of many foods and cultures throughout the world, and the result of their spiciness is all due to evolution, with over 3,000 varieties of chilli available across the globe, varying in size, shape, colour, heat, and flavour. As scientists continue to discover more about chilli peppers, they will forever feature prominently in many people’s daily soups, stews and stir fry’s.

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Bac(teria) to the future!

Considered one of the greatest medical breakthroughs in history, antibiotics have revolutionised the last century, saving an estimated 200 million lives since their discovery. Yet with each dose they add to one of the most pressing challenges in healthcare: antibiotic resistance.

This is where bacteria and other microorganisms evolve mechanisms to overcome, or resist, the effects of antibiotics which they were once sensitive too. It occurs naturally within the environment, but the excessive and inappropriate use of antibiotics in modern medicine is accelerating the process. On top of the 700,000 deaths resistance causes worldwide each year, it’s set to end an extra 10 million lives annually by 2050. There is a huge global research effort to try and rapidly discover new antibiotics. But the solution to the resistance crisis may have already been known for over a century— using viruses called bacteriophages to kill bacteria.

Bacteriophages are naturally occurring viruses that target and kill pathogenic (disease-causing) bacteria. They’re actually the most abundant life form on Earth and were first discovered in 1915.

After extensive research they were soon developed into treatments for a range of diseases—collectively known as “phage therapy” – but this didn’t last for long.

Scientists were also investigating antibiotics during this time, and by the mid1940s penicillin had been mass produced to such an extent—largely for use in the Second World War—that it quickly overshadowed bacteriophages. Phage therapy was abandoned and virtually forgotten… except in one place.

Tbilisi is the capital of Georgia and home to the Eliava Institute, a centre for phage research founded in 1923 by scientist George Eliava. Whilst the rest of the world abandoned bacteriophages in

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HILARY 2019

SAMUEL SUSSMES

favour of antibiotics, here they persisted. With limited access to antibiotics in Stalin’s isolated Soviet Union, Tbilisi became the leading centre for phage therapy, still operating to this day.

Since the collapse of the Soviet Union in the early 1990s people from all over the world have travelled to Tbilisi, receiving phage therapy for chronic infections that antibiotics seem unable to cure. This offers hope that phages may be able to treat the antibiotic resistant superbugs which are emerging across the globe.

Bacteriophages work in the same way as other viruses: they find a specific bacterium, inject their genetic material inside, hijack the cell’s machinery to make copies of themselves, and then break open the cell to release all the replicated viruses. These then attack other bacterial cells until the infection is cleared. One of the major advantages of bacteriophages over antibiotics is that they are incredibly specific—they only attack one particular species of bacteria. Antibiotics attack all bacteria in the body, including our beneficial gut flora, whereas a course of phage therapy only targets the specific bacteria causing the disease. This maintains our body’s useful bacteria, reduces side effects, and lowers the chance of developing further infections.

However, the specificity of bacteriophages is also a weakness. Phages will only attack certain bacteria, and so we must know which bacteria is causing an infection before treatment can begin. This process can take several days or even longer: a patient’s sample must be analysed, the pathogenic bacterium found, and the correct phage match found in the lab. In medical emergencies time is vital, and therefore broad spectrum antibiotics, which attack many types of bacteria, may be a better option when the identity of the pathogen is unknown. In addition, some infections involve multiple different pathogens, and one bacteriophage will not be able to kill all the harmful bacteria.

Scientists at the Eliava Institute have

attempted to overcome this problem by making collections of phages known as “phage cocktails”. These contain multiple phages, so can overcome multiple species of bacteria at the same time, or attack a species of bacterium from a variety of angles. For some infections there are pathogens that are commonly responsible for causing the infection—phages for these bacteria can be pre-manufactured into a cocktail and given to the patient as soon as they present to the clinic. These cocktails then start to clear the infection even before the bacterium’s identity has come back from the lab.

In the same way that bacteria can evolve to become resistant to antibiotics, they can also evolve to become resistant to phages. However, unlike antibiotics—which are not living organisms—phages can mutate alongside the bacteria, overcoming any evolving bacterial resistance. For this reason, phage resistance is not as problematic as antibiotic resistance; researchers can just wait until a new phage has evolved in the laboratory that can counter the phage-resistant bacterium. Selection of a new evolved phage is a relatively fast process— completed in a matter of weeks—compared to discovering and developing new antibiotics—a process which currently takes somewhere in the region of a decade.

Despite being almost exclusively confined to Eastern Europe, phage therapy is now starting to resurface in the West. A range of clinical trials have been conducted, with some promising results, but progress is slow. There is still an avoidance of phage therapies, both by drug companies and by the public. The general negative perception amongst the public is that treating an infection with a virus—in essence another infective agent—could be dangerous.

Whilst phage therapy is generally safe there is always the chance that phages could mutate during treatment inside the human body, just as viruses mutate and evolve in nature, and start

CHALLENGES

attacking human cells or triggering immune responses. Many scientists say that the greatest hurdle to overcome is regulatory, as phages are biological agents that come with this evolutionary unpredictability. Drug companies are also reluctant to work with phages.

They are concerned about patenting therapies that have already existed for so long, and can foresee trouble gaining regulatory permission to carry out trials using viruses with potential to evolve. As a result, phage therapies are still only approved in Eastern Europe, Russia, and a minority of other states across the world.

In the last 20 years or so research has led to a new type of antibiotic approach that could harness phage therapy’s benefits whilst avoiding their regulatory constraints: enzybiotics, in which enzymes derived from phages are used to attack bacteria. If phages are allowed to evolve in the laboratory and produce an enzyme that can overcome resistant bacteria, then this isolated and purified enzyme would not be classified as a biological product.

Perhaps using phages directly is limited, but their enzymes may give rise to a whole new class of antibiotics able to keep up with bacterial resistance.

Although still largely restricted to Eastern Europe where it is sold over the counter in pharmacies, its continued use in these countries offers hope that phage therapy may become a contender in the fight against bacterial resistance. Realistically, phages are not going to replace antibiotics altogether. Antibiotics are cheap, more effective in acute settings, and work most of the time. However, what the Eliava Institute has shown is that phages may have a role in treating chronic illnesses that antibiotics just seem unable to

cure. Maybe they will be the final bullet in the fight against bacteria, or maybe they’ll provide us with new enzyme-based methods of treating infections. Whatever their role, perhaps it’s time for this century-old therapy to finally go viral.

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CRISPR BABIES – What Now for Gene Editing?

On 26th November 2018, Dr He Jiankui, a geneticist based at the Southern University of Science and Technology in Shenzhen, China, announced the birth of the world’s first gene edited babies - two girls called Nana and Lulu. Using the gene editing technique CRISPR-cas9 to cause targeted mutation in genetic sequences, Dr. He mutated a gene called CCR5.

CCR5 encodes for a protein which HIV can use to enter and infect immune cells, and those with a naturally occurring CCR5 mutation are resistant to HIV. Dr He’s motivation was to reduce the incidence of HIV infection in China, where it is both highly prevalent and socially stigmatised. At the 2nd International Conference of Human Genome Editing (ICHGE, 2018) Dr He appeared to show that one of the

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girls has had both copies of the CCR5 gene disabled, potentially rendering her immune to HIV infection. Dr. He’s announcement has sent shock waves throughout the scientific community.

Gene editing of embryos is known as germline editing. Germline mutations can be passed down to all future generations.

Although the details of this experiment are unclear since Dr. He released the news via social media channels rather than scientific journals, his announcement has challenged the scientific community to assess current regulations regarding the use of gene editing techniques.

Although gene editing techniques have been around since the 1970’s, technical limitations as well as ethical considerations have prevented germline editing.

However, with the development of CRISPR-cas9, enabling quick, accurate and cheap editing of genetic material, it is apparent that germline editing is now only restricted by ethical considerations.

The first ICHGE in 2015 was established in order to bring gene editing experts together and establish usage recommendations with regards to CRISPR-cas9. Human

HILARY 2019

germline editing was strongly discouraged due to the associated risks of potentially harmful off-target mutations, incomplete editing of embryo cells, the unpredictability of interactions between genes and the environment, and the possibility of genetic ‘enhancements’ leading to social inequities. They called on major academies (United States National Academy of Sciences, the Royal Society in the United Kingdom, and the Chinese Academy of Sciences) to establish a set of common guidelines which scientists could use to self-govern their use of gene editing techniques, and to dissuade ‘rogue’ scientists from carrying out potentially harmful experiments.

Scientific self-governance has been historically effective at curbing ethically dubious experiments since self-governance is self-rewarding within the scientific community.

Failure to self-govern can lead to loss of professional standing, loss of funding and inability to publish, effectively stalling a career. Self-regulation has gained increasing importance in recent years due to the rapid development of scientific breakthroughs and limited scientific knowledge within legislative bodies. Global legislation is difficult to develop and implement due to differences in the legal standing of embryos between countries. The most significant attempt at a global directive on

EMMA MEE HAYES

germ line editing is a recommendation for a voluntary moratorium from the International Bioethics Committee.

Therefore, countries rely on local guidelines to ban research deemed unethical. However, guidelines are less enforceable than laws and lack negative consequences if broken. They can also vary widely between countries. For example, in Canada, germ line editing is criminalised and carries the threat of a fine and potentially imprisonment.

Though this might appear to be the most appropriate option, as technology moves forward Canada may find itself unable to implement new gene-based therapies as they would have to repeal a law rather than update a guideline.

In the United States, germ line editing is not banned. However, the National Institute for Health will not accept clinical trials involving germ line engineering and federal legislation prohibits government funding being used in germline editing research. In China, a report entitled Ethical Guidelines for Human Embryonic Stem Cell Research (2003) states that modified embryos may not be used for reproduction, but the practice carries no punishment under law. Overall, legislation regarding germ line editing is relatively relaxed given the associated risks. Formalising germline editing legislation will present significant challenges; however, public safety must be prioritised.

In 2015, Chinese researchers edited the beta-globin gene in

non-viable embryos using CRISPR-cas9. A mutation in this gene causes the blood disorder beta-thalassemia. Although the study had ethical approval and used donated non-viable embryos which were never intended to be implanted, both Nature and Science refused to publish the research on ethical grounds. China has been striving to improve its scientific reputation – for example they co-sponsored the first ICHGE which set out ethical guidelines regarding CRISPR-cas9 gene editing. However, Dr He’s research has once again cast doubt on the integrity of Chinese research, much to the frustration of other Chinese scientists. 120 Chinese researchers have signed a letter which described the experiment as ‘crazy’ and lamented the ‘huge blow to the international reputation…of Chinese science’.

This is not the first time that the gene editing field has had to deal with controversial research.

In 1999, Jesse Gelsinger, a healthy 18-year-old with a metabolic condition, died following a severe immune reaction to a virus used to deliver a gene which it was hoped would correct his condition. The repercussions of Gelsinger’s death reverberated throughout the gene editing field and delayed the field by a decade due to cancelled clinical trials and stricter regulations. Public confidence in gene editing was shaken.

Gelsinger’s death continues to hang over the field, and researchers and regulators are still cau-

CHALLENGES

tious of initiating human trials.

Ironically, Dr He cited this case at a previous conference urging caution as ‘a single case of failure will kill the entire field’.

Researchers are now concerned that the consequences of Dr He’s work may have a long-term negative impact and delay the development of new therapies. While there are risks associated with every new therapy, there are also major benefits which are illustrated by the treatment of blindness and certain forms of cancer.

Ensuring safety and confidence in CRISPR-cas9 based therapies was always going to be an issue given the previous failures of gene-based therapies, but the negative press incurred due to Dr He’s experiment has put the field on the back foot once again with regard to public perception.

Acting against ethical norms and undoubtedly well aware of the risks to the children and his own career, Dr He still decided to push ahead with his experiment.

Though Dr He will have to take responsibility for this decision, the fact remains that the circumstances he took advantage of enabled this to happen. The field of gene editing has faced and will face many challenges from the difficulties associated with legislation and public perception.

Though the gene editing scientific community seem willing and able to face these challenges head on, Dr He has made an already challenging future even more challenging.

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MICHAEL ORRELL

Fraud-ian slips: misconduct in biomedical sciences and how to prevent it controversial paper was fully retracted in If science is the pursuit of truth, then sci- 2010 – forever condemned with a large red entific misconduct is the perversion of that watermark – and in the same year Wakefield higher goal. In recent memory there have was struck off the medical register. Howevbeen several high profile cases of scientif- er, he has a presence in America where he ic fraud in biomedical research. This article now lives, and he sowed public mistrust in will explore some significant recent cases of vaccines in general that has failed to fully research misconduct in biomedical sciences go away. In the 21st century there have been (outside of drug trials), the effects they had, notable outbreaks of preventable infectious and what can be done to combat fraudulent diseases that the MMR vaccine controversy behaviour that tarnishes the image of re- must take some of the blame for. search.

Frustratingly, focus on Wakefield’s misFirstly, it’s important to be clear on what is conduct, as well as the negligence of his meant by scientific misconduct. For medical co-authors (an aspect that seems to get little research, the British Medical Journal for ex- attention), that can be easily backed up by evample uses a set of guidelines of fraudulent idence can get side-lined by a narrative of an behaviours including plagiarism, data falsi- outsider fighting the establishment. To prefication and other forms of deception, and vent a similar occurrence, more needs to be this should provide a framework of what is done to present the facts clearly to the public obviously bad practice. and to sniff out fraud much more quickly.

Where better to start considering these One consolation is that the misconduct practices than the MMR vaccine contro- didn’t directly cost the lives of any of the reversy? In 1998, Andrew Wakefield and his searchers involved, unlike in the sad story of co-authors published a paper in The Lancet the STAP cell controversy. STAP stands for that, based on data from 12 children, im- stimulus-triggered acquisition of pluripoplied a link between autism (and gut pathol- tency and describes a method of producing ogy) and the measles, mumps and rubella pluripotent stem cells from typical cells using (MMR) vaccine. A media firestorm followed methods such as acid exposure. Pluripotent and MMR uptake in the UK fell over several stem cells are incredibly useful in biomedical years before beginning to recover. The Sun- research as they can differentiate to form a day Times journalist Brian Deer was instru- variety of different cell types, and this could mental in bringing down Wakefield after he be harnessed for therapies for diseases that identified a huge conflict of interest: Wake- are currently challenging to treat. Such cells field and the Royal Free, where the key work are difficult to obtain, so devising straighthad been done, had applied for patents for forward protocols for generating them would single shots that could have been used to re- have been quite extraordinary, and no doubt place the combined vaccine whose safety he would reward pioneers with fame, prizes and was questioning. precious funding.

Furthermore, it was found that the inforSadly, it was too good to be true. The work mation about the children published LEFT in the by Haruko Obokata and colleagues on STAP study had been manipulated, as there wasdesigncells An early for a at the RIKEN Center for Developmenprosthetic, mechanical a mismatch between the gut pathology retal Biology (CDB) in Kobe, Japan, resulted arm. Designed by ported in the paper and the actual patholoin16thtwo papers in Nature in January 2014, Ambroise Paré, century. gy reports from the Royal Free Hospital.

The but other scientists struggled to replicate the Credit: Wellcome Images

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findings. Furthermore, it was found that embryonic stem cell lines at the lab were genetically indistinct from the proposed STAP cell lines, with the implication of contamination in the experiments described in the papers.

The STAP cell concept perished, Obokata was found guilty of misconduct and the papers were retracted. The case had a deep impact on research in Japan following the media storm that ensued, with some labs at the CDB moving elsewhere or being closed following the recommendation of a RIKEN reform committee. Other co-authors were deemed to have failed to identify problems with their papers rather than necessarily being guilty of misconduct themselves.

In August 2014, Obokata’s supervisor, Yoshiki Sasai died by suicide following the fallout from the controversy. His obituary in Nature notes his importance in organoid research and the tragic loss that had occurred.

Perhaps a key lesson to be learned here is the importance of damning those that actually commit fraud and sufficiently isolating this from the criticism of colleagues that could have done more to prevent bad science from getting published. A failure of this, combined with misdirected media attention, evidently ruins lives.

The previous two cases highlight rather extreme malpractice, whereas one might suspect that the more minor transgressions such as those by chromosome biologist Yoshinori Watanabe are more commonplace. In 2016, several of Watanabe’s publications in major journals came under scrutiny for doctored images amongst other issues, and a whistle-blower dossier demonstrated even more evidence of misconduct. This included image duplications within figures, suspiciously similar bar lengths in supposedly different histograms, digital removal of unwanted parts of images and even some impossible standard deviation values. Watanabe was dismissed from the University of Tokyo and is being scientifically “rehabilitated” at the

Francis Crick Institute for a brief stint.

Almost as disappointing as the fraudulent behaviours themselves is the defence of them. In the Watanabe case, the idea that corrections to the various problems identified in some of his papers didn’t affect how the results were described or the overall conclusions of the papers is beside the point.

In similar controversies embroiling other scientists, similarly weak excuses such as loss of the original data in question and implying that the proper presentation of controls doesn’t matter (amongst others) can be found.

From the cases above, going forward it is important to think about how further misconduct may be better identified and prevented. Journals and the mainstream media need to be more mindful of the motivations that can underlie misconduct, whether that’s financial gain or the more commonplace desire for positive findings where they may not exist. Identifying fraud is time-consuming, and it is disappointing how sometimes it takes individuals on the warpath to do vast investigational legwork when co-authors and journal editors are in better positions to more efficiently stop bad science being published.

It is also evident that a careful approach is needed to punish scientists appropriately and in a timely fashion: the path from the publication of Wakefield’s paper to its retraction was far too long, while draconian measures against labs even slightly associated with major misconduct cases may be excessive.

Finally, bad science starts with the researcher, so it may be that better education early in a scientific career about misconduct may help prevent further controversies, and as shown in the Watanabe case, some people think that even some guilty parties are not beyond redemption. However, effective responses are still needed to uphold the values of science and the public’s perception of it.

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Cure-ious about cancer We must understand our enemy in order to destroy it

Mutant powers

“A cure for cancer” is a phrase that’s thrown around time and again as one of the hottest pursuits in medical research. And for good reason: it’s the second biggest cause of death worldwide, after heart disease, and will affect one in five men and one in six women in their lifetimes. We pump billions into cancer research in the quest for a cure, but despite spending vast amounts of time and money, we are yet to find the miracle treatment. If there’s one thing we have learnt for definite though, it’s that cancer is a very tricky disease to treat.

“in spite of cancer’s frustrating complexity, huge progress has been made in both our understanding of the disease and in the development of potential treatments.”

Cancer arises due to mutations in cells –changes to their genetic material– which culminate in uncontrolled cell growth and division. Usually, in adults, cell division balances the rate of cell death so that our bodies, and all the things inside them, stay the same size. But when cancer cells start dividing uncontrollably, this balance is upset, and a lump of cells called a tumour can form. If this tumour is able to grow, it can affect functions of the tissue or organ where it is situated, or in late stage tumours, some of the cells can spread via the blood and cause secondary cancers elsewhere. Tumour growth and spreading can impair crucial body functions, making cancer a potentially fatal disease. However, cancer doesn’t have to form a tumour to be harmful.

Blood cancers result from proliferation of mutated blood cells, which can impair the immune response and increase vulnerability to infection.

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SHAKIRA MAHADEVA

One big unhappy family

Even though we might talk about a single “cure for cancer”, cancer is not just one disease. There are over 200 types –from blood cancers like leukaemia, to lung cancers and brain tumours– and as each of them are different, it is becoming increasingly apparent that we can’t apply a one-size-fits-all approach to treatment. This hasn’t stopped us trying though; traditional cancer treatments chemotherapy (anticancer drugs) and radiotherapy (using high energy rays to kill cancer cells) are widely used across many cancer types, and they do work. They aren’t perfect though: for some cancers these treatments are highly effective but in other cases their success rates are mediocre. There is a definite need to tailor treatment to cancer type if we are to take this disease down.

A distinctive property of cancer is that the cells responsible are our own, turned against us. It can therefore be very difficult to target treatments to kill tumour cells but not our own ‘self ’ cells. It isn’t even as simple as a binary distinction between tumour and non-tumour cells, as aggressive tumours can have multiple populations of slightly different cancerous cells. This is known as tumour heterogeneity and it means that treatment that works on one cell population may have no effect on another. And even once a treatment has been found for one cancer cell population, we can’t bank on it working forever. Cancer cells constantly evolve and adapt, changing their characteristics to yet further evade our attempts to kill them.

A weapon that lets us fight our own battles

All of this seems to paint a pretty bleak picture. However, in spite of cancer’s frustrating complexity, huge progress has been made in both our understanding of the disease and in the development of potential treatments. A breakthrough attracting a lot of attention, in the media and among scientists, is immunotherapy. Indeed, the 2018 Nobel Prize in Medicine was awarded to two scientists, James P. Allison and Tasuko Honjo, who pioneered the research in this field. Immunotherapy involves harnessing the body’s own immune system to fight cancer. For a long time it was a mystery as to why the body didn’t do this in the first place: surely if our immune system just did its job, cancer wouldn’t exist. It turns out that cancer has many tricks up its sleeve to shut down the immune system. Developing immunotherapies involves working out what these tricks are and creating drugs that stop them, so the immune system stays switched on and can destroy the cancer cells. This is exactly what both Allison and Honjo did, although independently of one another. They identified proteins on the surfaces of T-cells –immune cells that selectively kill damaged or infected self cells– which acted as ‘brakes’ on the immune system. They found that cancer cells had mechanisms of activating these ‘brakes’ to evade an immune response. As a result of their research, drugs were developed which blocked the ‘brakes’, enabling the T-cells to attack the cancer. These drugs are called checkpoint inhibitors and the two that came out of Allison and Honjo’s work are now in use in the clinic, with many other checkpoint inhibitors currently going through the clinical trial process.

CHALLENGES

In the works and just might work

The discoveries made by the Nobel Prize-winners have paved the way for a whole host of immunotherapy possibilities. One of these is known as “adoptive cell transfer”.

It is a newer technique than checkpoint inhibitors and is still in its research stages but has great potential for treatment of many types of cancer. It involves taking some of a patient’s T-cells out of their body and ‘training’ these cells to eliminate their cancer. If we could then select the T-cells with receptors that specifically recognise the patient’s type of cancer and, crucially, not their self cells, we could reinsert these T-cells into the body and eliminate the disease. Even more excitingly, we could use the same process to build up a library of T-cell receptors for every type of cancer. This would mean that for each patient, the appropriate receptor could be inserted into their cells to give their immune system the necessary weapon to kill their specific cancer.

Cancer has outsmarted us for many years. It turns our own cells against us, has many variations, and is a master of shape-shifting to dodge treatment. We are hot on its tails though, and as our knowledge of the disease continues to increase, and breakthrough treatments like immunotherapy progress through clinical trials, we are moving closer to those once elusive cures.

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Better therapies through engineering

An Oxford PhD student has been awarded a poster troscopy to understand the drug-framework prize at an international conference, and a Brazilian interactions from a vibrational point of view. graduate scholarship for her work on MOFs. Barbara said: “Attending conferences is one

Although many drugs present excellent performance against certain diseases (e.g. skin cancer), their inherent drawbacks (poor water solubility and instability in the circulatory system, leading to many side effects) limit greatly their application. Now, imagine such an approach that could facilitate the treatment of many serious diseases (e.g. cancer) that enable the precise attack on tumor regions reducing the length of treatments and their severe side-effects on normal tissues? That is what the second-year DPhil student Barbara Souza and her research in the Multifunctional Materials and Composites Lab are focusing on. Barbara has accepted the challenge of using Metal Organic Frameworks (MOFs), highly tunable and porous compounds, to perform the encapsulation of anticancer drug molecules. She is working on making MOFs more benign by using strategies that allow the encapsulation of therapeutic agents in the pores of the framework in one-step processes, with the minimum use of toxic solvents. Barbara’s research aims to deeper understand the interactions of anticancer drug molecules and MOFs, a key factor in controlling the speed and regulating the release of therapeutic agents. To accomplish this, Barbara has been applying Inelastic Neutron Scattering and Synchrotron Technology in collaboration with scientist working at the ISIS Neutron and Muon Source and the Diamond Light Source, in Harwell.

Recently, Barbara has presented the first results of her research at the MOF 2018, an International Conference on Metal-Organic Frameworks and Open Framework Compounds, held in Auckland, New Zealand, that was attended by over 600 delegates. She has been awarded the prize of best poster presentation. At the conference, most important one in the field, Barbara presented the use of a facile mechanochemical method (free from the use of toxic solvents) employed in the synthesis of the framework and encapsulation of the guest drug molecules; and she demonstrated the promising application of neutron spec28

of the most exciting things for DPhil students.

During these events we get the chance to present our research and exchange ideas with renowned scientists from around the world and other DPhil students. It is a great opportunity not

only to development contacts and possible collaborations, but also to make yourself and your research known among your fellow colleagues.�

Barbara was awarded a Brazilian graduate schola rship to pursue her studies in Oxford. She is grateful to FAPEMIG, the Minas Gerais State Agency for Research and Development, for funding her graduate studies. As a next challenge, she is actively taking steps towards translating the MOF technology into societal impact, focusing on the developing of multifunctional composites. An appropriate mixture of MOFs with a biocompatible polymer would yield a tailorable nanocomposite system, combining the unique physico-chemical properties of MOF nanoparticles with improved control of the premature degradation.

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NOAH HEARNE

The disaster memo

A look at the US Presidency’s preparations for catastrophe in 1969

‘IN EVENT OF MOON DISASTER’ reads the first line of William Safire’s 1969 memo.

Most memos are not written in preparation for one of history’s greatest possible disasters. Most memos are not an answer to one of those innumerable and tragic what-ifs that arise when trying to put man on the Moon.

This memo was drafted by the presidential speechwriter of Richard Nixon. This speech was to be delivered to a grieving planet. Nixon would have spoken Safire’s words to the American people if the astronauts America sent to the surface of the Moon, Edwin Aldrin and Neil Armstrong of Apollo 11, were not going to come back down in the command module which took them up.

Hopes were high, but the chances of the mission failing in this primitive space age were not low enough. Thus, one of the president’s staff suggested that such a speech be written, as morbidly as it seems, just in case.

‘Fate has ordained that the men who went to the moon to explore in peace will stay on the moon to rest in peace,’ reads the memo’s first line. The president would focus on the importance of constellations, courageous figures of myth, to stargazers of ancient times, and, with the entombment of two men on the Moon, how our heroes, ‘those epic men of flesh and blood,’ would be recalled and remembered by those looking out into the night sky today.

Nixon’s words call to mind those of Carl Sagan, as he describes the origin of life and the evolution of humans from matter created by distant stars: ‘…ultimately, [humans] set out for the stars from which they had come…we are star stuff that has taken its destiny into its own hands’. And this is true, for if those men were trapped up on the Moon and could not come back, we would see men in the stars, just as they have been throughout human history, and we would ‘know that there is some corner of another world that is forever mankind.’

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AMITY ROBERTS

Nancy Roman, ‘Mother of Hubble’ NASA Astronomer, Has Died Aged 93 Amity Roberts remembers a ground-breaking scientist.

Nancy Roman, a boundary-breaking astronomer known as the ‘Mother of the Hubble’, died aged 93 on December 25th, 2018.

Roman was NASA’s first Chief of Astronomy and supervised the planning and development of the Hubble Space Telescope that would change the way we see the universe.

Roman was born in Nashville, Tennessee and developed an interest in the natural world as a child. Her interests expanded to include astronomy when her family moved to a part of Nevada with low enough levels of light pollution to allow for star gazing. Here, at the age of 11, she was captivated by the stars and was determined to become an astronomer. This goal proved difficult during school, as she was faced with the assumption that only men become scientists. However, she remained determined and graduated with a degree in astronomy in 1946.

Three years later, Roman earned a PhD in astronomy from the University of Chicago, but she continued to struggle as a woman in science. It was at NASA in 1959 that she finally felt treated equally to men. Roman was the first woman to hold an executive position at NASA, joining just six months after the agency was established. She was instrumental in obtaining early funding for the Hubble by relentlessly pitching the project. She travelled across the US, meeting with astronomers and engineers to come up with an instrument that best suited their ambitions.

In 1990, eleven years after Roman retired, the $1.5 billion telescope was deployed by astronauts aboard the space shuttle Discovery.

It was a painstaking process, but it ultimately resulted in the deployment of the first major optical telescope to operate in space.

Roman budgeted and developed numerous smaller space observations, but it is the Hubble project that she is most remembered for. Following her career at NASA, Roman became a consultant and a champion of fellow women in science. Roman remains an inspiration to women in science and her legacy will be remembered for generations to come.

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