The Oxford Scientist: Perspective (#6)

Issue 6

Oxford University’s independent, student-produced science magazine.

Michaelmas Term 2019

Perspective

the Oxford Scientist

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2

www.jakemp.com/careers

Perspective

Contents Editorial

6

Einstein at the Patent Office Maria Violaris

8

Collaboration: Reforming Research Megan Boreham

10

From Nietzsche to Nissan Asher Winter

12

A Global Threat to Humanity: Anti-Microbial Resistance Cynthia Hou

14

To GM or not to GM? Elizabeth Tatham

18

Schools Competition

19

Cecilia: The Tale of Two Elements Jake Pugsley

20

Gene Editing Emma Mee Hayes

23

Personalised Medicine Sandra Adele

24

Particle PiĂąatas Sparshita Day

26

The Fault in Our SNPs George Williams

28

Obesity and Sweet Tooth Syndrome Angela Sichen Liu

30

The Controversial World of Animals in Research Anonymous

Team Editors-in-Chief Atreyi Chakrabarty Emma Lalande Print Editor Owen Yunaputra Kosman Web Editors Shakira Mahadeva Sandra Adele

News Editors Thomas Hornigold Denis Lan Creative Director Sophie Littlewood Events Manager Thea Beadle Business Manager Daisy Southern School Liason Jacqueline Gill

Sub-Editors Noah Turner Pandora Dewan Gloria Gao

OSPL

5

Alice Evans Elizabeth Tatham Anna Bassadone Ciara Stern Linus Milinski Jessica Lorimer Ishaan Kapoor Nicole Hasler Cynthia Hou

Chairperson Christopher Sinnott

Technical Director Antonia Siu

Managing Directors Elara Oakes Hung-Jen Wu

Non-Executive Director Angus Brown

Company Secretary Annabel Bainbridge

Directors Daanial Chaudhry Serena Parekh

Finance Director Maggie Wang Legal Director Annie Fan

Marina Smith Oscar Baker India Barrett Katie Birnie

Copyright Š The Oxford Scientist 2019

3

the Oxford Scientist

Join our senior editorial team for HT20 Editor-in-Chief Manages the production of the magazine, liaises with the rest of the editorial and managerial team, has the final say on all editorial and creative decisions.

Web Editor Runs our website blog and is responsible for site maintenance.

Creative Director

Print Editor Commissions articles for the magazine, and leads the team of sub-editors.

News Editor

Designs all aspects of the magazine and commissions

Leads the news team, who write news

illustrations from a team of artists. Experience with

stories for the print issue and the

InDesign is highly desirable. Oversees designing of

website throughout the term.

publicity material and other creative decisions.

Join our managerial team for HT20 and TT20 Business Manager

Events Manager

Leads the business team in securing

Leads the events team in organising

advertisements and sponsorships for

events through term and overlooks

the magazine and events, and manages

publicity and marketing for the Oxford

school subscriptions.

Scientist.

Other ways to get involved If being a part of the committee isn’t for you, there are plenty of other ways to get involved which might be up your street.

We always appreciate interest in writing - you can think about a topic for submission when the call for pitches comes out for each new issue, or send us a more ad hoc article for the blog. Our News writers and OxSci reporters write short posts about current events and progress in Oxford and further afield, and there are even opportunities to create themed podcasts.

Our new initiative, Chalk Talks, is a friendly students-for-students event where undergraduates to postdocs give short presentations on their ongoing research. It’s a great place to informally practice talking about your work and answering all sorts of questions from an academically diverse audience, and another fun way to get involved.

Email editor@oxsci.org to apply

4

Perspective

Editorial S

cience is no longer the absolute truth. It In a globalising world, it becomes crucial to provides us with models and possibilities to share,

represent

and

integrate

different

piece together our view of the world. perspectives in science. Collaboration is far from

Scientific study and discoveries are crucial in a dirty word. We need to be open to harnessing shaping our day to day lives and our futures. inspiration from others to advance our ideas.

Now more than ever, science relies on human From Einstein’s greatest theories being inspired perspective to guide its development and impact by emerging technology in his day, to the feats on society. What kind of a future do we want?

of modern-day particle physics, advances in science are more meaningful when we embrace

Perspective defines our everyday, and is of interdisciplinarity and share.. utmost importance in the realms of science.

‘Perspective’ can alter interpretations of the same With

rapid

scientific

technological

data set, or determine the prognosis and advancements, ethics also becomes omnipresent. diagnosis of a patient’s ailment. ‘Perspective’ can From appreciating applications of GM foods to add value to a research endeavour or make it the tech innovation of driverless cars, the highly

controversial.

Inherently-biased

by acceptance of advancing technologies varies on

nature, it is in our hands to try to sustain the an individual, societal and national basis. Animal methodical logic and precision associated with research has always been controversial when it science and the pursuit of knowledge. As such, comes to ethics for the ‘greater good’ - is it all how scientists apply their own perspective, and worthwhile? appreciate different angles, influences presentday progression, and the world as we know it.

Medical progress is deeply intertwined with scientific study, and with innovation becoming

Our understanding of the building blocks of life more specialised, perspective comes into play is improving in leaps and bounds. The Human again. With the advent of personalised medicine, Genome Project opened innumerable doors for the antibiotic crisis and the intricacies of disease us to explore the realms of our genes. While gene development we are only starting to appreciate therapies are in reach, we also have to grapple how an interdisciplinary outlook could help with the emerging technologies of DNA testing solve more problems than we expected . and gene editing. New scientific breakthroughs in this field will empower us to significantly We welcome you to the MT19 Issue of The reduce human suffering and we may no longer Oxford Scientist, and hope you enjoy the be limited by our bodies. Yet, does this put us in thought-provoking danger of pursuing perfection?

articles

within...Perhaps

they’ll even change your perspective.

Atreyi Chakrabarty and Emma Lalande, Editors-in-Chief

5

the Oxford Scientist

Danielle Edmunds

T

Einstein at th

he Bern town clock chimes: once, mechanical synchronisation of time, triggered twice, three times. Yet another patent his famously powerful thought experiments in

on clocks sits at the desk, this one claim‐ special relativity. The subject of one of the Annus

ing originality for sending time through tele‐ Mirabilis papers, special relativity is based on the phone

lines.

It

was

the

age

when notion of time being relative to the motion of an

electromechanical devices were starting to be observer, assuming constant speed of light. One used to synchronise distant clocks. From the particularly important thought experiment for comfort of the patent office, a young Albert Ein‐ this paper was about a moving magnet and a stein was again thinking through the subtleties of conductor. For this, it was vital to understand measuring time.

electromagnetic induction—a phenomenon that

After finishing his studies in 1900, Einstein frequently appeared in his patents. could not get accepted anywhere for a teaching

Armed with a detailed knowledge of the

post. Eventually he was offered a job by his patent process (see figure), Einstein spent his friend’s father at a Swiss patent office in 1902, fragments of spare time inventing, and filed over where Einstein’s task was to look through inven‐ 50 patents during his life. Try a quick Internet tions, check their originality, and write clear pat‐ search of Google Patents for ones by Albert Ein‐ ents to protect the inventors’ new ideas. His job stein. Several interesting titles and illustrations

“Einstein described the patent office as his ‘worldly cloister’, where he ‘hatched [his] most beautiful ideas’”

come up, from Light-intensity self-adjusting camera to Refrigeration. There is even a Design for a blouse, which has two methods of button‐ ing —who knew fashion and physics could inter‐ sect? Einstein believed that ‘the origin of all technical achievements is the divine curiosity and the play instinct of the working and think‐ ing researcher, as well as the constructive fantasy

lasted from 1902 to 1909, during which time of the technical inventor’. Yet as well as the joy Einstein published his four Annus Mirabilis (mir‐ of inventing, Einstein had some more practical acle year) 1905 papers. Einstein described the motivations: by selling the rights for the patents patent office as his ‘worldly cloister’, where he to companies such as Electrolux, he made extra ‘hatched [his] most beautiful ideas’.

Many historians speculate that the numerous

money to fund his research.

While Einstein’s patents did not become

patents Einstein analysed, relating to the electro- commercialised during his lifetime, his Refriger‐ 6

Perspective

he Patent Office

ation invention resurfaced in the 21st Century. term ambition of providing a portable “back‐ This 1930 patent had its origins in tragedy, when pack” for transporting blood and organs for a failed refrigerator seal led to a Berlin family be‐ transplants. Unlike Einstein, Broadway has stated ing killed by toxic fumes. Einstein and fellow explicitly, ‘I don’t think it should be patented to physicist Leo Szilard were then motivated to restrict use’, as ‘It should be a basic human design a refrigerator without deadly gases or right…to have a vaccination’. So, it seems Ein‐ moving parts that could fail. The advent of more stein’s fridge design may not quite make it back powerful commercial refrigerators with non- to another patent office. toxic gases meant this invention never gained

Viewing Einstein’s work from the perspect‐

popularity, but several aspects make it of interest ive of the patent office, his abstract theoretical to modern society.

Einstein’s refrigerator is powered only by a heat source, without electricity, whereas normal modern refrigerators use an electric pump (caus‐ ing the audible “hum” from a kitchen fridge).

Hence, it can be directly adapted to have renew‐ able sources of energy such as solar power. Fur‐

“Einstein’s physics influenced his patents, and patents influenced his physics”

thermore, in the words of Prof Malcolm breakthroughs become connected with the prac‐ McCulloch, an electrical engineer at Oxford, tical technological advances of his era. This ‘No moving parts is a real benefit because it can shows an interdependence of technology and carry on going without maintenance. This could fundamental science to push each other for‐ have real applications in rural areas. In 2008, Prof wards—Einstein’s physics influenced his patents, McCulloch led a team that set out to build a more and patents influenced his physics. As I sit writ‐ efficient version of Einstein and Szilard’s original ing this article at my desk, digital patents filling design, using pressurised butane gas and solar my laptop tabs, I hear a town clock chime three energy.

times. I wonder what novel thought experiments

The modern applications of ideas based on Einstein might have performed in the same seat, Einstein’s fridge have even led to prizes. In 2016, over 100 years after his own patent office days, 22 -year-old designer Will Broadway won the surrounded by the inspiring inventions of 2019.

James Dyson Award for his design of an absorp‐ tion refrigerator. His aim was to keep vaccines

Maria Violaris is a physics undergraduate at Magdalen

cool in developing countries—but with a long-

College.

7

the Oxford Scientist

Collaboration: Reforming Research M

ost researchers’ response to the word ‘collaboration’ is overwhelm‐ ingly positive. Many of the most influential scientific breakthroughs that have gone on to shape today’s scientific landscape have been the

product of collaborations: Gates and Allen, the Wright brothers, and Watson, Crick and Franklin, to name a few.

The global value of collaboration can be seen best in worldwide projects such as the Human Genome Project, by far the world’s largest biological collab‐ orative effort. The project combined work from 20 universities in six countries to map the 92.1% of the human nucleotide sequence, with the work using pub‐ lic funding from the National Institutes of Health and multiple other interna‐ tional research groups.

Alongside physical collaboration, software development has also aided a more inclusive scientific approach. The Open Science Framework (OSF), cre‐ ated in 2013 by the Center for Open Science, encourages the production of

8

Perspective publicly available projects by allowing research‐ searchers. In these cases, collaboration can often ers to register them, from individual experiments be dangerously entangled with vested interests. to the research goal of an entire lab, in a way that

Take the example of CRUK with their latest

allows their progress and contributions to be re‐ campaign, ‘Obesity causes cancer’, causing social corded easily.

media outrage with perceived fat-phobic im‐

The merits of collaboration have not only been agery. Many claimed that the company disreg‐ supported by large scale and well-funded pro‐ arded other influences of obesity risk, implying jects such as the OSF, but also verified by a range obesity is a choice, and the anger was further of individual studies, usually taking the form of fuelled by CRUK’s connection with Slimming systematic reviews. One paper, investigating the World as a donor, leading to conflict of interest importance of collaboration in creating influen‐ accusations towards CRUK. tial research, found a positive correlation

In July, Cancer Research UK (CRUK) pro‐

between the number of named contributors and voked social media outrage upon revealing their the number of citations the paper gained. The latest campaign ‘Obesity causes cancer’, with gi‐ physical distance between the collaborators’ ant posters of cigarette cartons with ‘Obesity countries even had a beneficial effect on the pa‐ causes cancer too’ plastered across them. Many per’s influence (as measured by citation level).

With so many benefits, it is hard to under‐ stand why some researchers may avoid collabor‐ ation. One reason for this may be concern over lack of recognition. This can become especially problematic if the terms of authorship are not agreed before the research commences. Grants and funding are often only awarded to individu‐ als so early career researchers may feel that col‐

claimed that the images were fat-phobic due to

“With so many benefits, it is hard to understand why some researchers may avoid collaboration.”

laboration is detrimental, given funding scarcity their suggestion that obesity is a choice in the and employment instability. But, with the cor‐ same way as choosing to smoke. The campaign rect levels of communication and effort, collab‐ disregarded other factors that influence an indi‐ orative work can provide a stepping stone to vidual’s risk of obesity, such as gender, race and

“The global value of collaboration can be seen best in worldwide projects”

income. This anger was fuelled by CRUK’s part‐ nership with Slimming World, the organisation donating over £14 million to the charity since 2013. By using money donated by a company that sells the promise of weight loss to fund re‐ search used to justify scaring people into losing

opportunity, providing both individuals and or‐ weight, CRUK found themselves in the middle ganisations with new insights and previously un‐ of a storm, facing accusations of a conflict of in‐ discovered pools of expertise.

Ask the same question about collaboration to

terest.

The key paper behind the campaign, pub‐

members of the general public and you may get lished in 2015, aimed to investigate the effect of a less positive response, especially when the word lifestyle factors on cancer risk, including obesity, ‘collaboration’ is combined with the word ‘sci‐ using Body Mass Index (BMI) as a measure. BMI ence’. Collaborations which affect the wider has already been heavily criticised by experts for population are often very different to those ex‐ being an ineffective measure of weight-related perienced by scientists. These collaborations, health, as it does not take into consideration perhaps between health charities, funding bod‐ muscle mass or fat distribution around the body. ies, organisations such as the NHS and commer‐ Ruth Travis, an associate professor and senior cial companies, have a far wider impact than molecular epidemiologist at the University of smaller partnerships between two groups of re‐ Oxford, stated, “Factors influencing BMI in in‐ Lucy King

9

the Oxford Scientist dividuals are complicated and there needs to be much more utive of CRUK, which called for the reconsideration of the research at lots of levels aimed at understanding how to campaign to ‘prioritise wellbeing over weight’. The letter limit excess weight gain as individuals age and reduce BMI was supported by fellows from both the University of in the overweight”.

Cambridge and King’s College London.

Despite the stark campaign slo‐ gan, the study also failed to prove a positive causal rela‐ tionship

between

With such controversies surrounding collab‐ oration, how can it continue to aid scientific progression in an unbiased manner?

high

Maybe the answer lies in transparency,

BMI and cancer. These

with a focus on making sure a level of

criticisms

were

high‐

lighted in an open letter from

nutritionist

Laura Thomas to

honesty is maintained throughout a project’s development, especially when research may be influen‐ tial in setting public policy.

the chief exec‐ Megan

Boreham

Biomedical

is

a

Sciences

undergraduate at St

Lu c

yK in

g

Hilda’s College.

From Nietzsche to Nissan ations of public attitudes towards ethical

quandaries posed by self-driving cars. In the

“Moral Machine" experiment, researchers cre‐ ated a game based on the famous "trolley prob‐

The ethics of self-driving cars

lem." Participants had to choose the most favourable result

from a series of rather gloomy outcomes in a hypothetical apid technological development has made self- car crash. The announcement of the experiment was a viral driving cars a reality. This advancement raises hit and led to millions of people from over 200 countries

R

questions about how these cars should make ethical contributing. This made the experiment one of the largest decisions in place of human drivers. While technology can ever studies conducted on moral preferences in popula‐

replace, and will undoubtedly supersede humans in actual tions. driving ability, driving a car involves moral decisions.

The "Moral Machine" experiment investigated nine These choices would have to be programmed—for instance different criteria including whether a self-driving car whether to collide with another vehicle or swerve towards should prioritise passengers over pedestrians, people over pedestrians in a crash. Such a circumstance would likely be pets, and youth over the elderly. Results were gathered by

exceedingly rare, but this, and similar situations, still need asking users questions such as: should the car continue for‐ to be considered as we move towards a future without a wards and hit a child, or swerve and hit an old lady? Here, human, in both the literal and metaphorical driving seat.

people had to consider both the ages of the potential vic‐ A study conducted by the Massachusetts Institute of tims along with the moral implications of changing the Technology (MIT) was one of the first large-scale investig‐ car’s trajectory.

10

Perspective Emma Brass

After four years, key results of the study were published walking"). Economic differences such as these were per‐ in the journal Nature, focusing on differences in moral haps the most notable with participants in countries with views between countries. Countries in close geographical higher levels of economic inequality showing greater gaps proximity and those with a similar culture and economy in their treatment of individuals based on their socio-eco‐ were likely to have closely aligned views. Indeed, three nomic status. This led Edmond Awad, a researcher in‐ dominant clusters of “moral alignment"' were seen: the volved in the study, to point out that policy should not West, the East, and the South.

necessarily just reflect public opinion: “It seems concerning

One prominent example in highlighting this geo‐ that people found it okay to a significant degree to spare graphical divide was the spread of countries that were more higher status over lower status. It's important to say, ‘Hey, likely to favour saving the young over the old. France was we could quantify that’ instead of saying, ‘Oh, maybe we the country most skewed towards sparing youth, with should use that.’” many European countries such as Sweden and Germany, as

Critics of the study have pointed out that the posed hy‐

well as the USA and Canada sitting above the average pothetical situations often seemed contrived. Having a bin‐ global preference for sparing younger lives. On the

“...a future without a human, in both the literal and preference for saving older lives. A similar split was seen in different countries’ propensities towards sav‐ metaphorical driving seat.” other hand, Japan, China, and Taiwan had a greater

ing the maximum number of people. More "individual‐ ary choice to make in a car crash, as was the case in the istic" cultures (typically seen in Western countries) were experiment, is exceedingly unlikely and indeed the number more likely to prefer saving as many lives as possible.

of crashes happening at all would be expected to drop with

Interestingly, when looking at people's preference for increased use of self-driving cars. Still, regardless of the dir‐ saving pedestrians over passengers whilst ignoring other ect usefulness of the data, it seems clear that the ''Moral Ma‐ factors such as age, these clusters seemed to break down. chine'' experiment has kick-started a dialogue surrounding Japanese and Greek people had on average a much stronger ethics which is necessary not only with regards to self-driv‐ tendency to avoid hurting pedestrians at the cost of the car's ing cars but within the field of artificial intelligence in gen‐ passengers than the Chinese and French participants did.

eral. When technology meets philosophy and public

These findings could have major implications for man‐ policy, answers are unlikely to be obvious even though our ufacturers of self-driving cars. The research also suggested lives and consciences will depend on them. that people in less economically developed countries were more tolerant of pedestrians crossing improperly ("jay‐

Asher Winter is a Chemistry undergraduate at St Hugh’s College.

11

the Oxford Scientist

A Global Threat to Humanity:

Anti-Microbial Resistance Antimicrobial resistance (AMR) is spreading at an alarming rate, yet the antibiotic industry is only shrinking—could a pre-antibiotic era return as our future?

A

ntimicrobials

revolutionised

medicine. antibiotic, resistance can arise. Moreover, resistant

Before antibiotics, the average life expect‐ bacteria have existed long before humans used an‐ ancy was 47 years. Infections such as tibiotics, even being found in Egyptian mummies

pneumonia could easily be fatal, and to put it from 9000 years ago. bluntly, a scratch could kill. There is no better ex‐

But now, resistance has become a threat com‐

ample than the First World War, where at least parable to climate change due to the overuse of an‐ one-third of soldiers were killed by infections and timicrobials. It is reported that 700,000 people die diseases.

every year due to resistant microbes. At this rate,

But now, the rise of antimicrobial resistance resistance could kill up to 10 million people each (AMR) makes it possible for the horrors of the pre- year by 2050, which translates to a devastating one antibiotic era to return. AMR includes antibiotic person every three seconds. The more we use anti‐ resistance, which is when bacteria survive expos‐ ure to antibiotics that usually kill or slow their growth. Resistance is present naturally in some bacteria and can arise due to random mutation, while microbes can also acquire resistance from others through gene transfer.

Antimicrobials are targeted at infections caused by

“Resistance is present naturally in some bacteria and can arise due to random mutation”

bacteria, viruses, and fungi, enabling us to treat microbials, the more resistance: by exposing life- threatening illnesses from tuberculosis to pathogens to antibiotics, selective pressure is ap‐ HIV, and malaria. Resistance not only paves the plied so that only resistant strains will survive and path for a future without such treatments, but it multiply, leading to greater numbers of resistant also means that common surgical procedures such bacteria. as organ transplants and C-sections will become

A prominent example of overuse is overpre‐

infeasible due to the high risk of infection. This scription. In 2016, the Centres of Disease Control risk is even larger for those with compromised im‐ and Prevention (CDC) reported that at least 30% mune systems, such as cancer patients undergoing of antibiotics prescribed to outpatients in the US chemotherapy.

were unnecessary, with more than 60% of respirat‐

Yet resistance is not new. Sir Alexander Flem‐ ory disease patients given antibiotics when not re‐ ing—the discoverer of the first antibiotic penicillin, quired. Antibiotics only work against bacterial warned us of this danger more than 50 years ago in infections, so taking them for a viral infection such his Nobel lecture. Fleming noted that if bacteria as the common cold will not do anything but drive were exposed to non-lethal concentrations of the resistance in the individual’s microbiome.

12

Perspective

Maria Kostylew

ing closer. At this rate, there would be no pharmaceutical companies develop‐ ing antibiotics by 2025. As Jim O’Neill the former-chief economist of Goldman Sachs puts it, we are ‘facing a growing enemy with a largely depleted ar‐ moury’.

This paradoxical situation results from decades of under-investment by companies and the government in anti‐ microbial R&D. Drug development is time-con‐ suming and costly, a single drug takes at least 10 years and 1 billion pounds to reach the patient. If it finally makes it to the market, new antibiotics are often re‐ served as a last-line defence. With

General practitioners still rely on agriculture and aquaculture. Although the patient’s symptoms and slow dia‐ they are needed to treat animal or plant gnostic tools such as a blood or culture infections, most of these including last-

“...its occurrence is not high enough to yield a sufficient market to sustain the development of new drugs.”

tests to distinguish between viral and line antibiotics, are instead used to pro‐ cheap, existing generic drugs still effect‐ bacterial infections. Better diagnostics mote organism growth or prevent po‐ ive enough, competitive pressure means such as the point-of-care C-reactive tential infections. that newly patented drugs are not sold As AMR becomes increasingly protein (CRP) testing have been trialled much. In other words, resistance is a in the UK. The test only requires a fin‐ deadly, it is critical that we reduce our problem, but with our present market ger prick, a few extra minutes, and a unnecessary demand for antimicrobials. system, its occurrence is not high cost of approximately £4, but it has not But even if antimicrobials were used enough to yield a sufficient market to proven effective in reducing unneeded completely appropriately, resistance as a sustain the development of new drugs. natural process can only be slowed prescriptions.

So it is unsurprising that no one However, such tests are yet to be‐ down, not eradicated. Therefore, not wants to develop antibiotics despite the come routine as it is still far cheaper and only do we need to make existing drugs urgent and increasing need for them. faster to prescribe antibiotics ‘just in stay effective longer by reducing use, Between 2003 and 2013, less than 5% of case’. Therefore, not only do rapid dia‐ the development of new drugs is essen‐ venture capital investments in pharma‐ gnostics need to be made available and tial. ceuticals were for antimicrobial devel‐ affordable to doctors, policies must be opment. With too little money and put in place to make such testing com‐ The Antibiotic market: a commer- market interest, too little time and nat‐ cial failure pulsory. ural resources, and the increasing threat hat being said, no new classes of But reducing antibiotic use in hu‐ of AMR and unpredictable occurrence, antibiotics have been introduced mans is simply not enough to tackle res‐ we need to focus on antimicrobial drug istance. The FDA reports that 70% of since the 1980s. R&D in antimicrobials discovery with renewed vigour and the antibiotics (by-weight), critical in is shrinking faster than ever, while the sense of emergency. treating human infections, are used in global threat of resistance is only loom‐

T

13

Economic solutions to an economic problem

T

he current system of antibiotic development and distribution needs changing, to align

commercial incentives with public needs. Accord‐ ing to the Review of Antimicrobial Resistance led by O’Neill, the heart of the problem is that the current system predicates drug profitability on their price and quantity sold. Therefore, it is critical to shift to a system that rewards innovation instead, based on its value to society. The review goes on to state that this could be achieved with a global ‘market entry reward’ system for antibiotics and alternative therapies. Companies that are successful in devel‐ oping a much-needed drug will be rewarded with a lump sum of 1.3 billion USD, effectively reim‐ bursing them for the high costs of drug develop‐ ment.

Of course, the funding must come from some‐ where. The Review argues that since effective an‐ tibiotics are widely required in the field, the whole industry should be involved in developing new antibiotics. This has led to the suggestion of an ‘Antibiotic investment charge’, where pharma

“it is critical to shift to a system that rewards innovation instead, based on its value to society”

companies not doing AMR-based research would be levied depending on their sales, while those in‐ vesting an equivalent amount or more would be spared - a ‘pay-or-play’ system. Those that are not doing AMR-related research would be levied de‐ pending on their sales, while companies that are investing an equivalent or greater amount will be

To GM or not to GM?

the Oxford Scientist

It’s not about the science.

I

n 1983, a gene from Agrobacterium (a plant-in‐ fecting bacterium) was successfully inserted into a plant cell, marking a 'coming-of-age'

moment for plant genetic engineering. The result‐ ing possibilities seemed endless; pest-resistant, selffertilising and nutritionally-fortified crop varieties.

But relatively little of this technology has been im‐ plemented on a global scale.

Casual viewers might think the technology is

not safe, which is understandable given the ‘frankenfood’ labels given to the new GM crops.

But this is a misconception as there is scientific consensus on their safety. The American Associ‐ ation for the Advancement of Science (AAAS) stated in 2012 that the ‘science is quite clear’ re‐ garding the safety of biotechnology for crop im‐ provement.

Demand for GM crops

T

he failure to integrate GM crops into main‐ stream agriculture is not due to lack of de‐

mand. In Tanzania, the loss of cassava crops due to virus outbreaks contributes to malnutrition and a shockingly high infant mortality rate. Tanzanian scientists have developed disease-resistant cassava strains that produce much greater yields than nat‐ ive varieties.

Despite this, Tanzania is one of many African

countries that has a ‘strict liability’ stance against GM crops. Even when the crops were tested in fields, ‘biosafety’ rules saw their destruction fol‐ lowing harvest—mere miles away from starving families.

spared. This would provide funding, and also but encourage AMR-related research to benefit the in‐

Why did GM fail?

dustry as a whole.

T

We must slow down resistance, reduce unne‐ cessary antibiotic demand, and boost new drug de‐

he science says that genetically modified (GM) crops are safe, so why doesn’t the pub‐

lic believe this? First impressions stick, and the en‐

velopment. We can outrace resistance if we act

trance of GM crops into the industry has shaped

now—and it starts with recognising resistance as a

the public perception of them ever since.

global threat to humanity.

The herbicide Roundup™, originally manu‐ factured by Monsanto, is one notable example.

14

Cynthia Hou is a Biochemistry undergraduate at Magdalen

The first GM product launched was Roundup

College.

Ready soy in 1996; this allowed soy farmers to

Perspective spray their fields indiscriminately without killing high temperatures and in arid environments. This the soy plants. This caused outrage over the effect has the potential to increase yields by up to 50%. of rampant herbicide use on the environment, and fears of the technology being monopolised by The future of food M is here to stay. But will it become the fu‐ large corporations.

The company could instead have developed a

G

ture of food? Proponents of GM draw paral‐

crop variety that produces a natural pesticide, lels between the processes of selective breeding and which would have reduced the need for spraying. genetic modification: both artificially alter an or‐ Had this been the case, today’s public perception of ganism’s genetic makeup to confer an advantage‐ GM might have been different.

ous trait. They argue that the differences between

Monsanto’s insensitive move, followed by today's staple crops and their wild ancestors are just fear-mongering from environmental activists, as ‘alien’ as changes created by GM. overshadowed other successful applications of GM

Moreover, some GM critics are starting to ac‐

in agriculture. These include Bt cotton, which is cept its potential use in publicly funded projects to genetically engineered to produce a natural insect‐ benefit small-scale farms as well as industrial ones. icide usually produced by soil bacteria. Although But GM, if it is the ‘future of food’, is not a silver bullet solution to the problem of sustaining the

“...relatively little of this technology has been implemented on a global scale.” the promised increase in crop yields has not been attained, partly due to disregard for practices to slow down the evolution of resistance, the figures for Bt cotton in India are not as low as activists have claimed.

In spite of such advances, public pressure has led governments to adopt anti-GM policies, such

world’s population.

Technologies such as Bt cotton in India must adapt to problems such as bollworms evolving im‐

“...the use of GM crops has rapidly expanded in developing countries, where potential benefits to farmers are most acute.”

as the EU’s effective moratorium on approvals of munity to the Bt cotton gene. This mirrors the GM crops; the process for evaluating new GM pattern of over-reliance on pesticides, creating an‐ crops is so slow that economic viability is limited. other monoculture. Just as flawed is the idea of Yet these same countries import GM corn for an‐ land-intensive organic farming, though promoted imal feed, revealing a disparity between the goals as the ideal solution by many environmental activ‐ ists. of campaigners and the actions of governments.

Nonetheless, the use of GM crops has rapidly

Instead, the ‘future of food’ should involve the

expanded in developing countries, where potential deployment of every feasible method to protect the benefits to farmers are most acute. Additionally, environment while maximising yields. With head‐ the potential of the bacterial viral defense mechan‐ lines detailing the stark reality of a burning ism CRISPR-Cas9 to edit genes was realised in Amazon and a changing climate, the public is be‐ 2012, accelerating the creation of new GM ginning to grasp that we must change, and this should include doing something different to reproducts.

Researchers at the University of Oxford are integrate our food system with a changing part of a team using this technology to engineer planet. rice with C4 photosynthesis, where carbon dioxide entering the leaf takes a more efficient route at

Elizabeth Tatham is a Biological Sciences undergraduate at St Hilda’s College.

15

the Oxford Scientist UKAEA kindly sponsors the Oxford Scientist

The UK Atomic Energy Authority to take a big step to fusion electricity

T

he world needs a new large-scale, clean, reliable energy source. With the increasing electrification of transport, the exponential increase in global energy demand, and the need for deep decarbonisation, we need to be bold in tackling these problems. Nuclear fusion – the process that powers the stars – can be a big part of the answer. It is low land-use, has effectively inexhaustible fuel reserves, less radioactive waste than nuclear fission, continuous supply and no carbon production.

The UK Atomic Energy Authority (UKAEA), in Oxfordshire, is helping to shape the future of energy production by hosting the world’s largest fusion experiment and tackling some of the key materials and engineering challenges to making a nuclear fusion power station a reality. We offer a supportive route throughout people’s careers, for example students undertaking summer placements at Culham, a graduate entry programme and post-doc development scheme.

In collaboration with the University of Oxford orking collaboratively with the University of Oxford has enabled us to find a significant overlap of research interests between the University and UKAEA. Our collaborations range from theoretical plasma

W

physics and mathematical modelling through to materials science and engineering. This breadth of connections creates a dynamic and exciting relationship which is continually growing and creating new groundbreaking discoveries. UKAEA supports many DPhil projects at the University and contributes specialist lectures to the Fusion Centre for Doctoral Training (a multi-university endeavour that includes Oxford Materials).

Fusion Power in South Oxfordshire hrough hosting the world’s premier fusion experiment – JET – on behalf of Euratom, and the UK’s flagship device, MAST Upgrade, combined with unique research capabilities, the UK is well positioned to lead the commercial development of fusion.

Using the power source of the universe in reactors

T

16

addresses this challenge, which continues to evolve and grow. UKAEA uniquely has a portfolio of facilities to address this challenge, which continues to evolve and grow. On top of our existing research programme, the UK

Government is committing £220M to the conceptual design of a fusion power station – the Spherical Tokamak for Energy Production (STEP). This investment demonstrates the UK Government’s commitment to fusion and recognises the central role UKAEA plays in the international fusion programme. STEP could result in the world’s first fusion powerplant being built in the UK – opening the way to a clean energy revolution.

This investment means that our collaborations with Oxford University are set to grow further, and we are

recruiting heavily in a wide range of disciplines. We take individuals from a variety of backgrounds and are able to offer opportunities across a number of programmes at UKAEA. For further information on the current opportunities available, you can view our list of vacancies at the website for UKAEA’s Culham Centre for Fusion Energy lab: https://www.ccfe.ac.uk/Jobs.aspx, or email recruitment@ukaea.uk.

You may also wish to submit your CV for any of our talent pools to be considered for future vacancies that arise.

Perspective

Case studies Chris Stuart - General Engineering, Cambridge, completed UKAEA’s 2-year graduate scheme, currently a real-time control and software engineer.

• I’ve been interested in fusion since sixth form. We had been taught about fusion as this vaguely abstract thing that happens in the Sun. I got a little bit obsessed and after reading pretty much everything about it, I realised there’s a Sun closer to home – there was a Joint European Torus (JET) experiment in the UK, that was the first place to do controlled DeuteriumTritium fusion reactions.

• Going through university I wanted to do something that was pushing sustainability. So UKAEA and JET just became something that was clearly a great fit for me.

• I would say in UKAEA there’s quite a focus on developing people. I didn’t have specific expertise in plasma physics, but I came with a set of skills that UKAEA thought was useful and they were very prepared to develop me and help me build more skills along the way.

James Buchanan – Physics undergrad and Particle Physics PhD, Oxford, completed UKAEA’s 2-year grad scheme, currently in the scientific computing group (HPC Specialist RSE) • I was looking for what I could do that would allow me to apply my skillset that I had developed during my PhD, whilst also finding something interesting and somehow meaningful. UKAEA was one of the first things I had stumbled across, and literally the day after handing in my thesis I thought “that seems really interesting” and I applied for their grad scheme.

• The work itself is intellectually interesting and fun to do, and I consider myself a lucky guy to be working in such a place. There’s also quite a lot of freedom with your work and you can pursue things that you’re interested in.

But also, it’s just a very nice environment to work in – a lot of the people that I work with are also my friends outside of work.

• Fusion energy is a very global endeavour and requires a lot of international collaboration, so we have a large European contingent that work here as well as colleagues from across the globe.

Lucy Kogan – Physics, Bristol, Particle Physics PhD, Oxford, currently a software engineer on MAST upgrade.

• The opportunities available on site are very broad. We have departments with scientists involved in the experiments happening on the reactors. Then we have staff working on the tools and analysis that supports that work, right down to the engineering roles developing control systems, designing parts for current and future tokamaks.

• Fusion is really cross-disciplinary. You need scientific research to push barriers, but for energy purposes engineering an implementation is one of the big challenges. We have everyone from mathematical modellers and theoretical physicists to material scientists, engineers and software developers.

• Viable fusion energy is definitely possible, it’s just that there is a lot of work to do! I think we are lucky to be working here, towards that goal.

17

the Oxford Scientist

Schools Competition We are pleased to announce the results of our Michaelmas

Winner

Term 2019 School Science Writing Competition. We re‐ Cecilia : The Tale of Two Elements ceived 254 entries from school students across the UK in Jake

Pugsley,

Year

13,

The

Cotswold

School,

Years 11-13, written to an incredibly high standard. The Gloucestershire topic of the competition was “an unsung hero of science”.

The winning article, selected by our panel of judges, was

Runners-Up

Cecilia: The Tale of Two Elements, by Jake Pugsley, Year 13, Ibn Sina: the Father of Modern Medicine...Who? The Cotswold School, Gloucestershire. Jake will receive a £50 Mahma Hyder, Year 13, Wisbech Grammar School, Amazon voucher. Eight runner-up articles were also selected Norfolk by our judges, and will be published alongside the winning article on our website www.oxsci.org.

Charles Richard Drew: the Father of Blood Banking Dionne Jeevarajah, Year 13, Norwich High School for Girls, Norfolk

Judges Ashvina Segaran is a breast surgeon in training who’s

decided to trade in the scalpel for a pipette. She is currently Edward W. Morley: the Michelson-Morley Experiment and its doing a DPhil in Clinical Medicine, and her research is on Successful Legacy of Failure obesity

and

breast

cancer;

particularly

the

tumour Kitty Joyce, Year 12, Oxford High School, Oxfordshire

microenvironment and nucleotide metabolism.

Jocelyn Bell Burnell: a Pulsar Pioneer Carolyn Ten Holter has a background in law, library science Divya Kartik, Year 12, Guildford High School, Surrey and communications. She now works on responsible innovation

techniques

and

her

research

focuses

responsible quantum computing.

on Glavny Konstruktor (the Chief Designer) Jakub Sypek, Year 12, Peter Symonds

College,

Hampshire Danielle Perro is a DPhil student in Women's and Reproductive health, where she focuses on endometriosis- Mileva Maric: Eclipsed by her Husband associated pain. In addition to her studies, Danielle is involved Krishna Gowda, Year 11, Merchant Taylors Boys School in science communication and uses her platform, whether it Crosby, Merseyside be twitter or FameLab, to talk about all things women's health, ranging from endometriosis to menstruation.

Yuan Longping: China’s Father of Hybrid Rice Christina Jiang, Year 11, The Blue Coat School,

Jacqueline Gill is a DPhil student in Evolutionary Merseyside Microbiology. She was a co-founder of the Oxford Scientist magazine, established the first national Oxford Scientist Alfred Russel Wallace: The Natural Selection for the Unsung school science writing competition, and has continued Hero of Science running the competition ever since.

Mirela Smolenska, Year 11, Benenden School, Kent

Should we focus on fixing our planet or move to a new one?

For a chance to win a prize and have your piece published in the Oxford Scientist, send us your thoughts as a 700-word essay

by Friday 24th January. Open to all UK students in Years 11 to 13. To submit, or for more information, email competition@oxsci.org go to our website oxsci.org.

If your school, sixth form or college would like to subscribe to the Oxford Scientist, please contact editor@oxsci.org.

18

Perspective

Cecilia: W

The Tale of Two Elements

hen I hear the term “unsung hero of science,” chemical elements, would never have been written without the first thought that comes to mind is of an un‐ Payne-Gaposchkin’s innovative approach. derrated, belittled researcher, his theses discred‐

ited by the wider world of erudition. I imagine a man, slumped at his desk, disparaged by his fellows’ baseless accus‐

P

ayne-Gaposchkin, herself, was quite the underdog. Born in 1900, her father died when she was just four, leaving

ations that his industry is uncorroborated or illegitimate. her mother to take care of the family alone. She won a schol‐ What doesn’t come to mind – yet what rightly should – are arship to Cambridge University, but was never awarded the the real unsung heroes, or, rather, heroines.

degree she earned because of her gender – a hardship many

Cecilia Payne-Gaposchkin is a perfect example. An elec‐ women faced until 1948. Attending a lecture by Arthur Ed‐ ted member of the Royal Astronomical Society while still dington in 1919 on his expedition to observe and photograph studying at Cambridge University, and the first person to stars as a test of Einstein’s Theory of General Relativity, the posit the idea that the primary composition of stars was he‐ flame, which was soon to become a flair for astrophysics, was lium and hydrogen (the two lightest elements), her disserta‐ ignited; she called it “a complete transformation in [her] tion was shunned by the leading scientists of her day, purely world picture.” She exchanged Cambridge, England, for because it contradicted the paradigms of her era. She also re‐ Cambridge, Massachusetts, leaving her home in 1923 to pur‐ vealed that such deposits of hydrogen were one million times sue a career at Harvard College Observatory. more abundant than on Earth, and thus it was the most com‐

There, she worked tirelessly for over 40 years, though

mon element in the entire universe. Nevertheless, this only not without competition. Harlow Shapley, head of the Ob‐ led her to be ridiculed further, since her results were so un‐ servatory, often pitted Payne-Gaposchkin against one of precedented and her thinking so unorthodox. In fact, even Russell’s mentees, Donald Menzel (yes, the same Russell she described her results as “spurious” due to their ground- again, who dismissed her astrophysical breakthrough). It was breaking implications and the imposed pressure of her peers.

only when Menzel succeeded Shapley as acting director of

It wasn’t until 1929 when astronomer Henry Norris Rus‐ the observatory in 1952 (and official head two years later) that sell – the very same man who rejected her research four years the competitors found common ground. Heart-warmingly, earlier – published his own identical findings in a paper that it was he who strove to improve her reputation, and he did so the theory became widely-accepted. If that wasn’t unfair markedly, eventually awarding her proper recognition as the enough, Payne-Gaposchkin’s discoveries are still often first female professor in the faculty, and head of the college ascribed to Russell, despite the opposite being true.

I

astronomy department.

Payne-Gaposchkin won the Rittenhouse Medal from the

n terms of significance, Payne-Gaposchkin’s work made Rittenhouse Astronomical Society at the Franklin Institute in metaphorical headlines, and revolutionised approaches to 1961, and lived to see her name immortalised in the field she

astrophysics across the globe. Otto Struve, arguably one of loved so passionately, as the ‘2039 Payne-Gaposchkin Aster‐ the most prolific astronomers to date, with over 900 journal oid’: a minor planet, in whose cosmic brilliance her legacy articles and books, pronounced it “the most brilliant PhD will live on forever. To further memorialise such an influen‐ thesis ever written in astronomy” – an accolade very few can tial pioneer and figurehead of modern day science, the Amer‐ flaunt. And it didn’t stop there.

ican Physical Society's Doctoral Dissertation Award in

Former contentions that the Sun’s elemental composition Astrophysics was renamed the Cecilia Payne-Gaposchkin was similar to that of Earth were therefore disproved, which Doctoral Dissertation Award in Astrophysics in 2018, to gave way to the major conjectures of stellar nucleosynthesis, kindle the solar flare of hope of the future unsung heroes – stellar lifecycles, and the astrophysics of supernovae. The and heroines – of science. famous B2FH paper – among the most cited in astrophysics history – which explored nuclear fusion and the origins of the

Jake Pugsley is in Year 13 at The Cotswold School, Gloucestershire.

19

Maria Kostylew

the Oxford Scientist

Gene Editing Now that we can - should we?

“Your scientists were so preoccupied with whether or not

CRISPR-Cas9 is a gene editing technique that allows for

they could, they didn’t stop to think if they should”. 25 years any region of the human genome to be specifically targeted on, this quote from Jurassic Park by the great Jeff Goldblum and edited. The field of gene editing was revolutionised. rings truer than ever. While every great scientific advance‐ Gene editing experiments were now quicker, cheaper and ment experiences some level of discussion and controversy, much more efficient. While the vast majority of researchers no field attracts more debate than that of human genetic en‐ used CRISPR-Cas9 to understand the basic functions of gineering. The development of Clustered Regularly Inter‐ genes or to target a specific disease-associated gene, there are spaced Short Palindromic Repeats (CRISPR)-Cas9 gene several researchers whose experiments fall in a more ethical editing technology has prompted more dispute than poten‐ grey area. tially any other biological technologies. Never before have

Human Germline Modification (HGM) is the deliberate

we had the ability to so easily and effectively change the hu‐ alteration of human eggs, sperm or embryos which will affect man genome—for better or for worse. CRISPR-Cas9 is for‐ not only the individual in question, but all future generations

“Are we as a society ready to grapple with the questions gene editing forces us to consider?”

of the said individual.

From the moment CRISPR-Cas9

technology was released, scientists were well aware that this leap forward in technological potential warranted a further debate on societal consequences of HGM both positive and negative. Thus, the first International Summit on Human Genome Editing was held in 2015. It was hosted by the

cing scientists, governments and the general public to assess Chinese Academy of Sciences and the UK's Royal Society the potential consequences of gene editing technology. Are and the scientific and ethical issues associated with human we as a society ready to grapple with the questions gene edit‐ gene-editing research were discussed. A group of global ex‐ ing forces us to consider: should all perceived disabilities be perts cautioned that HGM could profoundly ‘alter future hu‐ cured? Will the likely cost of gene editing widen social in‐ man societies’, and ‘exacerbate existing inequalities in equalities? Are we ready to be able to control human evolu‐ society’. Though not against the idea that CRISPR-Cas9 tion rather than leaving it to chance ?

20

could be used as a preventative treatment for genetic diseases,

Perspective

What is CRISPR-CAS9?

Deoxyribonucleic acid (DNA) is a long thin molecule shaped like a double helix. DNA contains all the information needed to create an organism. This information is in the form of a code made up of 4 nucleotide bases called adenine(A), thymine(T), cytosine (C), and guanine(G). The cell 'reads' this code and transcribed to RNA (a single strand of nucleotides). RNA is then translated into amino acids which makes up all the proteins that a cell needs.

Similar to the way that letters combine to form words, DNA bases combine in specific sequences to make genes. For example, eye colour is controlled by sixteen different genes. Small changes in the genetic code, called mutations, can sometimes occur. These are usually harmless.

However, there are also many diseases caused by mutations in critical genes. These include mutations in the CFTR gene, causing Cystic Fibrosis, and in the BRCA gene, which greatly increases the risk of developing breast cancer.

CRISPR-Cas9 is made up of the enzyme Cas9 and a length guide-RNA (gRNA).

Cas9

A specific genetic sequence on the gRNA guides Cas9 to a specific gene.

Cas9 acts like molecular scissors and creates a break in the DNA, which can disable the gene and stop it working.

gRNA

CRISPR-Cas9 can be used to repair a dysfunctional gene by introducing a new piece of DNA with the correct sequence which inserts between the two breaks caused by Cas9.

CRISPR is continuously improving but...

CRISPR therapy can treat Sickle Cell Anaemia.

CRISPR-Cas9 is not 100% efficient so not all cells may be edited.

Healthy red blood cells carry oxygen around the blood via haemaglobin.

However, in patients with Sickle Cell Anaemia - mutated heamoglobin leads to misshapen blood cells which clump together causing anemia and severe pain.

Scientists use CRISPR-Cas9 technology to reactivate fetal haemoglobin, restoring the normal shape of red blood cells and reducing symptoms.

Similar clinical trials using CRISPR technlogy to target cancer and blindness are currently underway.

Most scientists agree to gene editing for fatal or incurable genetic disorders.

However, some scientists believe that there should be no restrictions on which genes can be edited.

Emma Mee Hayes

Different genes can have similar DNA sequences. This could cause Cas9 to be directed to the wrong gene.

CRISPR editing of embryos is highly controversial.

“Designer babies” are children who have been genetically edited, particularly with regard to traits such as intelligence, athleticism and appearance.

Creating “designer babies” by editing the genes of embryos is very controversial, as it impacts every cell in the body and all descendants.

At the International Summit on Human Genome Engineering, international experts generated guidelines for use of CRISPR-Cas9 including the recommendation to not genetic edit any embryos until both technical and ethical issues had been addressed.

Dr He Jianku disregarded the recommendations of the summit and create the worlds first genetically engineered children in November, 2018.

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the Oxford Scientist the report from the conference was cautious. It stressed that level of gene editing, nor do we know all the genes involved at the time in question it ‘would be irresponsible to proceed in the desired traits, it is imperative that the ethics and limits with any clinical use … unless and until (i) the relevant safety of “designer babies” be established before we can do it. It is and efficacy issues have been resolved … and (ii) there is likely that HGM—whether carried out via CRISPR-Cas9 or broad societal consensus about the appropriateness of the pro‐ other methods—would be extraordinarily expensive and posed application’. Despite the clear advantages CRISPR- therefore restricted to those who could afford it. This would Cas9 has over previous gene editing techniques, not all safety and technological hurdles have been overcome. Though HGM was not banned, the conference recommended that a voluntary moratorium be put in place until the aforemen‐ tioned issues were resolved. Broad societal consensus had not and has not been reached with regard to gene editing-based therapies, and regarding non-disease associated gene editing, there is even less consensus.

“The ethical and societal consequences of gene editing technology are farreaching and will require worldwide discussion and collaboration...”

Announced days before the second International Summit prohibit CRISPR-Cas9 technology from being spread on Human Genome Editing, the scientific community was equally across all socioeconomic brackets, potentially creat‐ shocked on the 28 November 2018 when Dr. He Jiankui an‐ ing a genetic aristocracy associated with better health, higher nounced the birth of the first CRISPR-Cas9 gene-edited skills and longer life. This would widen existing socioeco‐ children, twin girls called Nana and Lulu. Dr. He disabled nomic inequalities. the CCR5 gene, which the HIV virus uses to enter and infect

And what about the designer babies themselves—would

cells. Dr. He’s experiment was met with nearly universal the biological advantages given to them correspond to a sim‐ condemnation, with scientists labelling his experiments pro‐ ilar social advantage? Some people are naturally gifted in cer‐ foundly disturbing and monstrous. Dr. He is not the only tain areas and this is applauded and celebrated. But what if researcher pushing the ethical boundaries of gene editing.

someone was born genetically enhanced for speed and won

Dr. Denis Rebrikov, a Russian scientist, has announced gold in the Olympics—would this be celebrated or con‐ plans to carry out similar experiments to Dr. He’s in children demned? at risk of contracting HIV in utero. But it is Dr. Rebrikov’s

Furthermore could gene editing technology force us to

other planned experiments that capture the ethical complex‐ decide on what we consider true humanity? Evolution (the ities of gene editing. He has revealed plans to prevent deaf‐ change in a population over successive generations) can in‐ ness in children born to deaf couples using CRISPR-Cas9. troduce drastic changes to a population, but these changes While deafness is classified as a disability, the line between can take thousands if not millions of years. Evolution is an disability and diversity is becoming increasingly lax. Many inherently random process highly influenced by environ‐ deaf individuals feel that curing deafness would rob them of ment. Advancements in gene editing allow for a more selfthe rich world of deaf culture and that attempting to “cure” guided approach as well as significantly speeding up the rate deafness is belittling and immoral. They are not the only of change. Could we end up changing swathes of the popu‐ ones to feel this way. Those with conditions such as dwarfism lation so much that they are seen as inherently different from or autism hold a similar view. This raises a serious question— humans—and if so, what would these changes be? should such conditions be cured or should the focus be on

There are no inherently right or wrong answers to these

increasing accessibility and societal acceptance? Targeting questions, nor can they be answered by one person. The eth‐ these conditions as something that needs to be fixed could re‐ ical and societal consequences of gene editing technology are inforce social stigma and is uncomfortably close to eugenics far-reaching and will require worldwide discussion and col‐ (promoting the improvement of inherited human traits laboration in order to reach a satisfactory conclusion that will through intervention).

harness the extraordinary potential of gene editing while pro‐

For some, the holy grail of gene editing technology is the tecting us from ourselves. infamous designer babies. Human embryos would be edited in order to create a more advanced individual, particularly

Emma Mee Hayes is studying for a DPhil at the Nuffield Department, at St

with reagrd to traits such as intelligence, height or athleti‐

Edmund Hall.

cism. Though we neither have the technology to achieve this

22

Perspective

Personalised Medicine What happens when one size does not fit all?

T

he first race-based combination pre‐

essential tool in medicine. The example of Ge‐

scription drug, Hydralazine-plus-ni‐

fitinib: Researchers observed that Japanese pa‐

trate is used in the treatment of

tients over-express a certain protein: Epidermal

congestive heart failure. Among African Amer‐

Growth Factor Receptor (EGFR). Gefitinib

icans, life expectancy of those with heart failure

works by inhibiting EGFR and consequently

is increased using this combination drug,

decreasing its activity. EGFR is a protein found

whereas white Americans respond less effect‐

in both normal cells and cancer cells. However,

ively to the drug. Another drug, Gefitinib, used

its over-expression can be a result of mutations.

in the treatment of certain cancers such as breast

efficacy and minimise side effects. However, in

“Therapeutics would be much easier if if the same dose of drug always produced the same response.”

reality, genetic and lifestyle variations between

These mutations can cause EGFR to be con‐

individuals, play a major role in how an indi‐

tinuously activated, leading to uncontrolled cell

vidual responds to a given drug. Personalised

division, one of the hallmarks of cancer. Using

medicine and Pharmacogenomics testing offer

this information, patients can be prescribed

the possibility of more precise therapeutics for

more personalised targeted therapy.

and lung cancer is more effective in Japanese than American patients as evidenced by clinical trials.

Therapeutics would be much easier if the same dose of drug always produced the same response. Enabling research to improve drug

several drugs and disorders. Personalised medi‐

The use of pharmacogenomic testing can

cine (precision medicine), is the concept of in‐

help healthcare providers determine the best

dividualising drug therapy using the genomic

medication for a patient. These tests can help

information of an individual. Pharmacogen‐

determine the effectiveness, optimum dose and

omics, also called pharmacogenetics or drug-

possible side effects of a drug. There are several

gene testing, focuses on how an individual’s

pharmacogenomic tests currently in use for this

genes affect their response to medication. This

purpose. One of these is the CYP2D6 genetic

is a field of intense research activity, rapid pro‐

test, which tests for variants of this gene, pre‐

gress and high expectations. However, proving

dicting how patients will respond to different

these tests add to present health diagnosis and

medications for the treatment of a variety of

improve patient outcomes remains a challenge.

conditions like breast cancer, depression and

As researchers continue to look further into

anxiety disorder. Information from this test

disease pathways and how drugs affect them,

shows how a patient will metabolise a given

personalised medicine has the potential to in‐

drug, which can affect their responsiveness to

crease the quality of clinical care and become an

it.

23

the Oxford Scientist Another pharmacogenomic test is the HLA-B gene test, which also tests for variants of a gene in patients. The HLA-B gene has several variations depicted by different numbers. For example, pa‐ tients with a HLA-B*1502 gene variant cannot take Carbamazepine to treat epilepsy and seizures, as they have a higher risk of developing adverse re‐ actions. Patients with a HLA-B*5801 gene variant can develop a potentially life threatening dermato‐ logical disorder called Toxic Epidermal Necrolysis if given a medication used to decrease high blood

“Personalised medicine and Pharmacogenomics testing offer the possibility of more precise therapeutics for several drugs and disorders.” uric acid levels. These pharmacogenomic tests are not widely used in hospitals, mainly due to con‐ cerns about costs, which can range from around £100 to £2,000. Another reason is due to the chal‐ lenge of showing how these tests results can be utilised clinically to improve patient outcomes.

As researchers continue to study genotypeguided drug therapies with the goal of improving clinical outcomes, some focus has been put on re‐ search that can help identify novel molecular tar‐ gets that drive disease progression in certain individuals. It is likely that these targets are relat‐ ively uncommon, and drug development will be difficult, but the benefits will be huge. In an effort to shed more light on the future development of personalised medicine, the Centre for Personalised Medicine at University of Oxford serves as a com‐ munication and engagement vehicle for students, academics, clinicians and the public to explore the benefits and challenges of personalised medicine.

Although much work remains to be done in the field, personalised medicine offers an opportunity to transform the future of healthcare.

Sandra Adele is studying for a Masters in Pharmacology at Green Templeton College.

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Particle P

How accelerators sweeten up the Standa

"T

here is nothing new to be discovered in physics now. All that remains is more precise measure‐ ment”. This famous quote by Lord Kelvin in

1900 spoke of a perspective shattered almost immediately by a stream of significant discoveries, such as the discovery of the electron in 1897, the nucleus of the atom in 1911, and the proton in 1919. Suddenly, our understanding of the “building blocks” of our world had completely changed. The atom, once accepted to be absolutely indivisible, was now just a doorway into an untouched realm of discovery. Throughout the years, a new model of the fundamental particles, forces, and interactions of the universe was developed: The Standard Model of particle physics. Behind the dawn and growth of this new era was the innovation of accelerators and colliders.

Accelerators focus and boost subatomic particles to higher energies and velocities using electromagnetic fields to produce well-focused and high-energy beams. In many ways, the utility of accelerators and colliders can be equated

“The atom, once accepted to be absolutely indivisible, was now just a doorway into an untouched realm of discovery” to piñatas. Only when you beat the piñata do you realise what is inside of it. Colliders operate on the same principle, with the impact being between two particle beams and the highly anticipated sweets corresponding to subatomic particles we might discover. The harder the impact, the more sweets come out. Therefore, if you handed a toddler the stick, you would get far fewer sweets than if a grown teenager were to beat the piñata open.

W

hat does all of this mean? We simply do not have ac‐ cess to studying many particles until we reach high

enough collisional energies. And just like the toddler needs time and funds to grow into a teenager, accelerators also need time and funds to advance and reach these higher potential collisional energies. Accelerator physicists are simply playing

Sophie Littlewood

Perspective

Piñatas

ard Model of Particle Physics

the role of parents and they are taking their role very seriously.

The Large Hadron Collider (LHC) in Switzerland is the largest collider in the world: a circular accelerator with a 27km diameter. Over the years, research conducted there and at other fa‐

“Behind the dawn and growth of this new era was the innovation of accelerators and colliders” cilities around the world have led to the develop‐ ment of an incredible database of fundamental particles. A recent triumph of the LHC was the confirmed detection of the Higgs boson, the particle that explains why matter has mass and whose existence was postulated in 1964 but had never been empirically shown.

Despite the brilliance of the current Standard Model, there are still large gaps in our understand‐ ing, such as the nature of dark matter and energy, accounting for a speculated 96% of the universe and also the matter antimatter asymmetry of the observable universe. Other key theoretical at‐ tempts include the unification of the four funda‐ mental forces of the universe: the Standard Model does not account for gravity, which has been ex‐ tensively described in Einstein’s general relativity.

Research into new accelerator technologies is in full swing to facilitate our search for evidence, and maybe even discover new physics.

Physicists at Oxford and several other univer‐ sities are actively involved in this effort. The Fu‐ ture Circular Collider (FCC) has been proposed to follow up on research conducted at the LHC, but with ten times the collisional energy. This will al‐ low them to both test long-standing hypotheses and raise new questions – the true essence of bluesky research.

D

espite their high collisional energies, circular colliders are not perfect. Accelerated charged

particles following a bent trajectory radiate away energy (synchrotron radiation). This means for lighter particles, like electrons, acceleration using a circular collider is not very effective unless the ra‐ dius is very large, adding massively to the cost of production. Circular colliders also need intricate systems of superconducting magnets to steer the beam and ensure collision. These colliders are also very expensive: the LHC cost around £3.85 billion whereas the largest linear collider, SLAC, cost £0.31 billion. Consequently, linear colliders, which accelerate in a straight line, are of significant interest even though they currently have lower energy reaches.

Certain phenomena are better studied at spe‐ cific energies, which are easy to miss if we search only at higher energies. Hence, the lower-energy reaches of linear colliders do not render them ob‐ solete. In fact, due to synchrotron radiation, circu‐ lar colliders usually deal with larger-particle collisions (like protons as at the LHC) whereas lin‐ ear colliders are able to study the same physics much more precisely due to cleaner signals and data. Designs for an International Linear Collider (ILC) and Compact Linear Collider (CLIC) have

“Despite the brilliance of our current Standard Model, there are still large gaps in our understanding...” been proposed to study various elements of the Standard Model and its contemporaries, such as more detailed measurements of the Higgs boson.

The FCC, ILC, CLIC are three cookies in a jar full of potential accelerator technological ad‐ vances. With several new methods still in develop‐ ment, the scientific renaissance of the 19th and 20th centuries that inspired our quest to discover the ‘truth’ of our reality is just the beginning. Al‐ though the piñata is yet to burst, we can be certain that whatever trickles out will be remarkable.

Sparshita Dey graduated from St John’s College with a Masters in Physics in 2019.

25

the Oxford Scientist

O

ne hundred and fifty years ago, in a called a SNP chip to rapidly examine 700,000 laboratory in Germany, a young sci‐ SNPs and determine their identity. They can entist named Friedrich Miescher iden‐ then compare how similar your SNPs are to

tified an unusual new chemical while studying other people’s or look for SNPs associated with white blood cells. At first scientists assumed it diseases. This process makes genetic test kits both was unimportant, but then they began to un‐ useful and potentially misleading. cover its remarkable structure: a double helix

DNA firms tout the promise of helping

held together like a zip by pairs of chemical people understand their health. Most test kits building blocks, nucleotides known by their ini‐ look at many SNPs associated with disease - the tials A, C, T, and G. Even more impressive, the most famous probably being BRCA. Mutations sequence of these nucleotides blocks encodes in‐ in the BRCA gene can increase a woman’s risk of formation about proteins, the workhorse mo‐ breast cancer from 12.5 % to up to 90%. Check‐ lecules of cells. Today, home testing kits allow ing for disease-causing variations seems like a anyone to access their DNA sequence. But with good thing. Knowing their risk allows women science racing ahead of public understanding of to take proactive steps like Angelina Jolie, who genetics, we risk misunderstanding and misusing had a double mastectomy when her BRCA this information–with worrying consequences.

mutation was found. However, the reality is not

By one estimate, 1 in 25 Americans had used so simple. one by 2017. Only a few among them, however,

In a recent paper, scientists at the University

actually understood how they work. The basis of of Exeter found that more than 84% of SNP chip these tests is the single nucleotide polymorphism results showing a rare mutation in the BRCA (SNP). This is a location in the DNA where the gene were actually false positives, suggesting that specific nucleotide widely varies among the pop‐ 84% of the women told they have a rare BRCA ulation. DNA testing companies use a device variant are healthy. SNP chip results can lead to

26

Tiffany Duneau

Perspective months of worry and unnecessary surgeries, genetic composotion is not accounted for, whilst which waste NHS time and resources and put arguably reinforcing culturally backward ideas women at risk of complications. Conversely, be‐ about nationality. This is especially worrying in ing told that your results do not show a problem today’s political climate where questions of iden‐ does not mean you are completely in the clear. tity are fraught. In Israel for instance, DNA test‐ Diseases like cancer and Alzheimer’s are genetic‐ ing is already being used to “prove” Jewishness ally complex and have been linked with millions before a couple are allowed to marry. of SNPs–many more than home kits test for. By

Home DNA testing offers everyone a

falsely scaring healthy people and falsely com‐ chance to learn about aspects of their genetic forting potentially sick people, misunderstand‐ make-up. However, that knowledge is useless ing of tests could prove a health disaster in the unless we have the right context to use it prop‐ long term.

erly. As these kits grow in popularity, the NHS

Alongside health, probably the most popular will have to reconsider the services it provides to use of home test kits is ancestry research, ex‐ ensure that people do not misinterpret or misuse ploited by tourism companies taking advantage their testing results. More broadly, our under‐ of a powerful need to understand our origins.

standing of what our genes mean for our place in

Companies achieve this is by taking samples society must change as knowing details about from different geographical regions and finding our genome becomes the norm rather than the out which SNPs are most associated unique to exception. A century and a half on, we are only particular places. DNA is then compared to these now beginning to fully reckon with the con‐ reference samples, giving a percentage similarity sequences of Miescher’s momentous discovery. score for each region. However, it is a question‐ able method for ancestry testing: many regions

George Williams is an undergraduate at New College.

are underrepresented, and the historic regional

The Dark Side of DNA Testing 27

the Oxford Scientist

Obesity and Sweet Tooth Syndrome Who is to blame?

O

besity

is

clinically

defined

Alicia Hayden

when strategies, we should examine who is to blame for

someone’s Body Mass Index (BMI) ex‐ this global crisis in the first place. ceeds 30. It is a metabolic disorder

Historically, obesity has been regarded as a

whereby energy intake from food and drinks ex‐ disease of irresponsible personal choices. Eco‐ ceeds energy consumption from metabolism and nomic growth and rapid improvement in living physical activities. There are many health-related standards suggest that we are better off, with our risks associated with obesity, especially for chil‐ purchase and consumption of food no longer lim‐ dren. This includes increased susceptibility for ited by financial ability. At the end of the day, our type II diabetes, cardiovascular diseases, and even calorie intake and physical activeness are down to premature deaths. In 2016, at least 650 million individual choices. We buy and consume more adults over the age of 19 and 340 million aged 5– unhealthy foods that contain high amounts of 19 were obese worldwide, which makes it a press‐ sugar, saturated fats, and salt. Individuals often fail ing global issue. Fortunately, as with most non- to recognise the long-term effects of overconsum‐ communicable diseases, obesity is highly prevent‐ ing energy-rich food and children are particularly able. But before we rush into preventative susceptible to this. 90% of households exceed the

28

Perspective Alicia Hayden

daily recommended dose of sugar intake and consumers are often not even aware of the sugar content of products.

Modern lifestyle, from the prolifer‐ ation of fast-food outlets to the abund‐ ance of automobiles, increases energy intake and reduces the need for physical activity, while long office hours leave little time for exercise. Also, takeaways are much more convenient and afford‐ able now, increasing the ease of extra consumption and encouraging sedent‐ ary lifestyles. These choices are key contributing factors to obesity.

H

owever, the food industry cannot escape its responsibility to this

obesity epidemic. Promotions, dis‐ counts, and marketing of food brands all encourage people to eat more and profit food companies. High sugar products commonly have more market exposure

Furthermore, social environments

and discount in price. Moreover, food can increase the tendency of becoming and drink portions are getting larger obese. Despite all of the campaigns for a over the past 30 years, increasing their healthier diet, the healthiest choice may energy content per portion.

not always be the cheapest or most ac‐

To reduce sugar content in pro‐ cessible option. Foods containing high cessed food, in 2015 the UK govern‐ levels of sugar are often the most afford‐ ment established a goal of a 20% sugar able. Consequently, cheaper foods are reduction in the food and beverage in‐ purchased and consumed more often by dustry. However, the vast majority of people in lower socioeconomic groups.

“In 2016, at least 650 million adults over the age of 19 and 340 million aged 19 were obese worldwide”

This creates a socioeconomic gradient such that there is a widening health in‐ equality between the rich and the poor.

S

o far, very little attention has been given to agricultural policies that in

fact shape diet through food availability and price. For example, the European agricultural

policies,

which

were

prompted by food shortages resulting

the industry has failed to meet this tar‐ from World War II, called for an in‐ get. Other countries have launched crease in the availability of energy dense sugar taxes in an attempt to reduce the foods, such as sugar, meat, and milk. consumption of added sugar, but there However, these policies have promoted is great resistance from the Food and an overproduction of these products, al‐

and diabetes. Examples of such policies include those on sucrose, which has been heavily protected by tariffs, min‐ imum price guarantees, quotas, and ex‐ port subsidies. In addition, the EU limited the production of high fructose corn syrup which is a substitute of sucrose, to 5% of all sugar production.

Together, these policies lift up the profit margin and encourage European farm‐ ers to manufacture sucrose, leading to overproduction. The resulting growth of the sugar industry has made half of the world’s ten largest sugar producers to be in Europe.

In an environment that is antagon‐ istic to healthy living choices, obesity should not be solely blamed on indi‐ viduals. The issue is complex. There‐ fore, we need solutions not only in public health, but also agricultural policies and education. We as individu‐ als, along with industry and the govern‐ ment must all engage in this battle, for the obesity epidemic to be defeated.

Drink Federation, which dismisses the lowing new public health concerns to tax as ‘political theatre’.

emerge within society, such as obesity

Angela Sichen Liu is a Biomedical Sciences undergraduate at St Hilda’s College.

29

the Oxford Scientist

The Controversial World of

Animals in Research A

nimal experimentation is one of the novative and life-saving science’. Animal research greatest ethical dilemmas facing modern has played a pivotal role in developing drugs that science. While animal research leads to have saved millions of lives. Animals give us the

life-saving

treatments,

to

anti-vivisectionists capacity for gene editing, exploring brain activity,

(people who oppose the use of animals in scientific and manipulating complex biological systems, all research) the practice is cruel and barbaric, regard‐ of which are ethically dubious in humans. Invari‐ less of its potential benefit to human health. But ably, some people do experience adverse effects what are the issues with animal research, and what when they take drugs tested on animals, but all is currently being done to overcome them?

prescribed substances have also been deemed safe

For years, Oxford University has been under in extensive clinical trials. Animal experimentation fire for using animals in medical research. Oxford therefore forms only part of the research frame‐ has one of the largest biomedical research centres work that integrates in vitro work, studies in hu‐ in Europe and undertakes the greatest number of mans, and epidemiological evidence. scientific procedures on animals annually. Natur‐

But animal research is not perfect, and there

ally, it is a hub of fierce anti-vivisectionist activity. are major issues translating findings into successful In the mid-2000s, protests led to violence over the clinical trials. This is partly due to the intrinsic construction of the Biomedical Sciences Building physiological differences between laboratory an‐ — a state-of-the-art research facility to rehouse imals and humans, as well as the experimental con‐ laboratory animals from around Oxford. There ditions under which drugs are trialled. Despite were arson attacks and bomb threats, and research‐ these differences, even fruit flies and nematode ers were even followed to their homes. Con‐ worms can be useful, due to biochemical pathways sequently, the University took out an injunction highly conserved throughout evolution. against specific animal rights groups to protect staff and researchers.

While claims of mistreatment are a mainstay of anti-vivisectionist campaigns, rigorous regulat‐

But opposition to the use of animals remains. ory systems govern animal research in the UK. In April 2019, a 400-strong protest marking the The Animals (Scientific Procedures) Act of 1986 40th anniversary of the World Day for Animals in regulates experiments conducted on animals, in‐ Laboratories called for an end to animal research in cluding a cost-benefit analysis on whether the po‐ Oxford. Protestors claimed that ‘50 percent of an‐ tential benefit to human health outweighs the imal experiments in UK universities are for curios‐ suffering caused. In fact, the UK goes above and ity's sake’, with a devastating 70,000 people killed beyond the EU laws on animal research, with Ox‐ or disabled by animal-tested drugs in England each ford’s ‘gold standard’ policy on welfare exceeding year. Moreover, animal rights activist Peter Egan both national and international guidelines. stated, ‘90 percent of all tests on animals as models for human diseases fail’. These statistics appear damning for the use of animal experimentation in science.

C

T

he other guiding principle of animal research is the 3 R’s – the replacement of animals by

using different experimental models, the reduction of the number of procedures undertaken on anim‐

ontrarily, Oxford describes its animal re‐ als by utilising better experimental design, and re‐ search programmes as at the ‘forefront of in‐ finement of procedures on animals to minimise

30

Perspective suffering. By following these guidelines, the total number of procedures conducted on animals re‐ duced by 7 percent since 2017 in the UK, with the number of non-human primates used in Oxford falling to only 10, compared to 52 in 2004.

Moreover, refinement includes group-housing several animals in a cage to replicate their natural social environment or using less invasive tech‐ niques. Not only do these principles improve an‐ imal welfare, they generate more reproducible data, meaning fewer animals are needed in the fu‐ ture.

As a DPhil student working with animals, these principles are hard to forget — improving animal welfare is at the forefront of experimental

design. However, to those outside the industry, there is a perception of secrecy that only encour‐ ages exaggerated claims. Consequently, Oxford University signed a Declaration of Openness on Animal Research, even letting BBC cameras film inside laboratories in 2014. Nonetheless, only 34 percent of the UK public feel well-informed about animal research, so more needs to be done to better inform the public about the realities of animals in science.

From my perspective, animal research is still necessary for much of the science being under‐ taken in Oxford. Furthermore, every individual I have met has the utmost care for the animals they use and do everything they can to minimise their suffering. Nevertheless, mounting social pressure to move away from animal experimentation will only accelerate the development of alternative

techniques, for example the use of human stem cells and computational modelling.

Although animal testing is still necessary and cannot yet be replaced, it is important to increase public awareness of the realities of animal re‐ search. Not only will this dispel myths dissemin‐ ated by anti-vivisectionists, but it will also better address the ethical controversies of animal exper‐ imentation.

Anonymous.

Danielle Edmunds

31

the

@oxsci @oxsci @oxfordscientist editor@oxsci.org

Oxford