Are we ready for the new era in genome editing?

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Biotechnology is advancing faster than ever and it is proving difficult for antiquated funding, patent, regulatory and communication systems to keep up.

Emerging drug therapies, improved medical devices, novel links to cancer and exciting laboratory techniques from industry and academia are published regularly across a broadening range of academic journals. Just last week Chinese scientists published research on their attempts to edit the genome of a non-viable embryo.

Genome editing involves the editing of the wealth of genetic material in our cells. One technique which is generating a lot of excitement among scientists is the application of CRISPR-Cas9 to genome editing in both somatic cells, the cells that make up our body, and germ cells, or egg and sperm cells. Unlike somatic cell engineering, which could be used, for example, to cure genetic diseases in an individual, germ line engineering could see genetic diseases such as Alzheimer’s or cancers eradicated across generations. Proponents of germ line engineering argue this potential, while critics warn of a slippery-slope including “designer babies”, children of the affluent selected on the basis of aesthetics or intelligence or physical ability, representing the darker and increasingly possible side of germ line engineering.

The highly effective and simple to use clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system was first discovered in a bacterium, Streptococcus pyogenes, as part of the cellular adaptive immune system. In short, CRISPR RNA is used by the cell to prevent infection by identifying foreign DNA that is later removed by the Cas9 nuclease, a native form of genome engineering if you will.

New studies

In March, two separate commentaries on germ line engineering appeared in Nature and Science. Both sought to bring the discussion on the use of genome editing in humans to light, particularly with regards to germ line engineering, while calling for different approaches on continuing research in this area.

Edward Lanphier and his colleagues, writing in Nature, argue for a temporary moratorium on research into germ line engineering. They cite the tenuous benefits of the technique, the restrictions by many European countries on inheritable genetic modification and possible public confusion as reasons against continuing research.

David Baltimore and his colleagues, writing in Science, more astutely recommend a conference on the scale of the Asilomar recombinant DNA conference held in 1975, the conventions of which are still impacting modern biology, including those on enhanced safety factors and recommendations on types of experiments. This proposed conference should pull together an international range of legal experts, ethicists, scientists (from graduate students to industry), policy makers and the lay public to discuss the challenges of germ line engineering. They also strongly discourage attempts at clinical applications of human germ line genome engineering and advocate for the creation of fora for scientists and bioethicists to come together and discuss the ethical, scientific and legal challenges of genome editing.

Although Edward Lanphier and his colleagues bring up valid concerns about the uncertainties and unknown dangers of germ line engineering, I would argue that this is reason for more research, not less, with more open dialogue as advances are made.

How close are we to editing genome in the germ line? It turns out, as simple and efficient as CRISPR/Cas9 is reported to be, that we still have some major technological hurdles to overcome. Last week’s paper by Chinese scientists, published in Protein and Cell, discusses their work on editing the genome of a non-viable human embryo. The research team, led by Junjiu Huang of Sun Yat-sen University, reported they were able to successfully edit a gene in a small fraction of their pool of embryos, but they came up against great technical and biological challenges, including significant off-target effects. They cautioned that further research into off-target effects and the cell’s own DNA repair mechanisms is sorely needed before we can move this technology to the clinic. The authors further emphasised the necessity for more analysis of the molecular mechanisms of CRISPR/Cas9 gene editing in humans. It is only a matter of time before their call is answered by other research groups around the world.

From the lab to the clinic

We have entered an era where it is possible, in a lab, to edit the human germ line, but there remain great challenges before this technology can be applied to the clinic. Germ line engineering holds great potential, but also great ethical and biological risk. The fact is, we simply do not know enough about biology, human or otherwise, to make predictions on the outcomes of multiple-gene editing in distant generations. By eradicating one disease, could we be selecting for another? Is germ line engineering taking evolution into our own hands with little regard for the consequences?

The global financial crisis that started in 2007 permanently altered the landscape of scientific funding and reengaged the public in discussions on funding priorities. Care is clearly needed for this research to move forward, but it would be hugely detrimental if leading research nations cut funding to genome editing techniques because of fear or ignorance. We must work to keep science open and transparent, but we must also continue with cutting edge research into fundamental processes that will give us a better understanding of inheritance, the genetic basis for disease and the implications of genome editing on organisms and communities. A new era in biology is here. The question is whether we are ready to embrace it.

*Paul Bergen [2013] is doing a PhD in Pathology. Picture credit: http://www.freedigitalphotos.net and ponsulak.

 

India’s Daughter and the importance of context

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India’s Daughter, Leslie Udwin’s recent and controversial documentary, honed in on the infamous Delhi gang rape of 2012, which has become a highly provocative and sensitive issue in India. Spurring protests across the country, this gang rape brought visceral responses from people across India. It seemed natural, then, to focus on this as a case study for analysing rape in India. Within the domestic context, such a provocative approach was beneficial to the extent that it initiated important conversations in the media and among the general population.

However, for a global audience, the documentary painted a simplistic black and white picture of a highly complex issue. The victim was an educated middle class girl with high ambitions. The perpetrators were uneducated and trapped in a cycle of poverty, with little hope for the future. The class divide could not have been shown in a more obvious way – but this is a narrow portrayal of rape cases. Furthermore, a focus on the graphic details of one particular act (which had already been repeatedly stressed by the Indian press), rather than the wider manifestation of rape across the country and the reasons behind it narrowed the vision of the film even more.

Such narrow portrayals often fail to bring forth into public discourse the more hidden forms of rape that exist in societies, such as domestic rape, child molestation by family members, date rapes and even rape of the socially marginalised by police and the armed forces. Any discussions of rape should consider these other crimes, often less explicit and therefore all the more in need of public discussion and discourse.

The film was screened recently at one of the Gates Cambridge Reel Interventions sessions, preceded by a highly thought-provoking and detailed introduction by Dr Priyamvada Gopal, a professor at the Faculty of English, Cambridge.

In the discussion that followed the screening it was not simply the film itself that was debated, but also the very context of the film screening. There seemed to be two key elements to this context: the international audience viewing the film and the fact that it was in a university setting. These helped articulate two widespread misconceptions about rape. The first is that rape doesn’t just exist in a separate, nebulous space in the outside – developing – world. An international audience has to be careful to avoid assuming that rape is something which happens ‘elsewhere’, when in fact it is a global issue. Rape is very much a reality all around the world.

Secondly, one of the arguments stressed in the documentary and in discussions, was that rape is chiefly the result of a lack of education. This generates the notion that it is only ‘uneducated’ people who are rapists while the educated are merely their victims. This argument was contradicted by research showing the very high occurrence of rape in educational institutions committed by people who often have degrees from top universities. It became evident that it was crucial that we, as students, should not dismiss the issue of rape as a problem only in the developing world, but that we should look at it in the context of the institutions that we are a part of. Rape is something that needs to be addressed in every community.

The screening and talk were highly relevant to the student community not only because they followed the widespread discussions that the documentary has raised in the media, but they provided a platform for students to discuss these issues in the context of a university setting.

*Neha Kinariwalla [2014 – MPhil in Modern Society and Global Transformations], Cillian Ó Fathaigh [2014 – MPhil European Literature and Culture] and Ananya Mishra [204 – MPhil in Modern South Asian Studies]. Photo credit: Nilroy and Wiki Commons.

The downside of moves towards gay equality

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In the last decade, we have witnessed a dramatic shift in public discourse about gay issues in the US and the UK. Throughout earlier gay organising, one thing was always clear: whatever else gays were, we were victims. At least, we were at risk of being victims. Victims of hate crimes, police brutality, discriminatory laws, family rejection, AIDS, suicide, conversion therapy, the Holocaust. Gays had No Future, and black comedy was a key part of How to Be Gay.

But with dramatic progress in the social and legal status of gays over the last decade, things are changing. Gays are no longer Longing for Recognition; we have it. Military service, parades and propaganda, prom dates, having sex, and most recently getting married are (mostly) legal and supported by a majority of the US and UK populations. Even The Gay Daddy is now literal. The HRC [Human Rights Campaign]- one of many gay lobbying organisations – reports annual revenues of over 38 million dollars

Some gays are still seen as victims. Those living in Russia and Uganda are subject to horrifying laws, and in Jamaican and Muslim communities they are also imperilled. But British and American gays are described as having forged Safe Space for themselves. Sometimes in school we’re told “Dude, You’re a Fag“, but It Gets Better when we go to a university in a big city.

Having it all?

We’ve come so far that some are even declaring The End of Gay, that the gay community is a myth, and that we’re now post gay. With gay victimisation overcome, little is left to unify gays in one identity. Unlike The Kinks, gay organisers have been arguing that we are like everybody else. We’re normal. At long last, it is possible for gay kids to live the same lives as their straight peers. School dances, weddings, raising children; careers in politics, military, and media – gays can finally have it all.

But a vocal minority of writers push back Against Equality and against The New Homonormativity. For them, the struggles of other queer people – whose bodies, genders, sexualities, bank accounts, and relationships don’t look like Dan Savage and Terry Miller‘s – are left out.

My research on queer university students (an ongoing study at numerous sites across North America) highlights another complication of the cultural shift from gay-as-victim to gay-as-normal. Even in the best of conditions, at wealthy universities in famously gay cities where It Gets Better, queers are sometimes still victims of violence, harassment, discrimination and hostility. And the desire to appear normal often leaves us silent about it.

It’s not that queer people are making a conscious choice to cover up victimisation to further assimilationist politics. Acts of bias and hate have stigmatising effects, and few want to be a victim. Even when we’re “out” and involved in LGBTQ organisations, we frequently cite the desire not to be seen as different as a reason not to speak up in class, not to complain about harassment, not to report offences, not to mention them to friends and family.

The shame of victimisation isn’t new or unique to LGBTQ people. It’s not a product of the turn toward assimilation. But when gay organising called on victimisation as the basis of community, identity and politics, it offered an empowering way to reclaim a positive sense of self identity from that fear and shame. While the current trend of gay assimilation offers unprecidented possibilities for living normal, safe lives, it offers little in the way of support for people who are still victimised. Where they once shared a community-defining problem, victims are now isolated. And with gay victimisation ‘solved’, little thought and energy goes into the ways sexual and gender minorities continue to be victimised, or the ways those harms disproportionately fall on the most marginal groups.

*Jeffrey Lockhart [2014] is doing an MPhil in Multi-Disciplinary Gender Studies. Picture credit: nongpimmy and http://www.freedigitalphotos.net.

What makes good chocolate?

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Springtime brings about an awakened sense of curiosity and desire to indulge the senses. Around this time of year we may be thinking about purchasing fresh flowers or luxury chocolate gifts. When it comes to chocolate there’s something to please nearly everyone: from the milk chocolate Easter rabbit to the dairy-free vegan bar. With such an abundance of choice, the hunt for good chocolate is really an exercise of intellectual and gastronomical exploration.

Certifications like Fairtrade mark, Rainforest Alliance, UTZ, Organic, and Vegan can make it seem like this decision is easier. Or they can make it downright confusing. These days consumers are so bombarded with eco-certifications, ethical awards, and health claims that it can be hard to tell which labels are actually doing good for ourselves, the chocolate makers and cacao farmers, and the environment. Many artisanal and truly high quality chocolate bars do not carry any conventional certification at all. What they carry instead is a story behind the bar.

A multidimensional global commodity

Chocolate is a fascinatingly complex global commodity. It intersects disciplines and sectors, addressing topics as diverse as global trade, agriculture, rural livelihoods, biodiversity conservation, commodities speculation, health and heritage. There are 49 major cacao-producing countries in addition to many smaller ones. Additionally, there is no single chocolate flavour. Even more than fine wine, chocolate has over 400 flavour compounds and its bouquet of flavours is influenced by thousands of decisions, from the soil in which the plant is grown to the final phase of processing. Colorful flavour wheels such as those developed by Chocopolis and TCHO can help give consumers a vocabulary to describe this diversity of taste.

However, there is a darker side to chocolate too. Large chocolate manufacturers monopolise the industry, yet the majority of cacao is grown by small-scale farmers who straddle the equatorial line and often the line of impoverishment. The spatial and technological divide between the farmers, the large chocolate companies and the consumers translates to a huge discrepancy between the final price of the product and the income farmers receive. There are also pressing environmental concerns. Cacao thrives in biodiverse hotspots such as the Amazonian region where shade grown forest ecosystems provide a habitat for birds, insects and other forest-dwelling organisms. Grown according to traditional organic methods free of agro-chemicals, complemented by prices that actually improve rural livelihood conditions, cacao can be part of the equation of environmental conservation and social justice.

Hidden gems

The rise of the craft chocolate market has transformed the ways in which the world sees chocolate as much more than a sweet confection. Beyond certifications, small chocolate makers are about forming meaningful relationships with the cacao farmers. They address the ethical concerns through a more transparent supply chain with labels such as “direct trade”, “bean-to-bar”, “single origin”, and “single estate”. They preserve the genetic diversity of the plant by seeking outstanding, bold flavours through fine aroma or heirloom cacao. They keep things simple by using fewer ingredients – sometimes just cacao and sugar – to stay honest to the consumers and honour the nutritional power of pure cacao. And most importantly, they are businesses that strive to do good for people and the environment. Good chocolate is ethical, ecological, and enjoyable.

With such diversity in flavour, country of origin, and type of manufacturing the choice of which chocolate to purchase can be surprisingly complex. When deciding which chocolate to purchase or gift away, there is no “best” chocolate. Certainly there are some not-good chocolates, namely those made with low quality raw ingredients and that are part of a larger industry of quantity over quality production. But perhaps one of the best (and most enjoyable) ways to discover good chocolate is to hunt for chocolate that tells a story. Ask with curious mind: Where was the cacao grown? Where was the chocolate manufactured? What’s the story behind the bar?

*Madeline Weeks [2014] is a Gates Cambridge scholar as an MPhil student in Geographical Research studying linkages between the production of shade-grown coffee and wellbeing of coffee farmers in Veracruz, Mexico. She also pursues a deep passion for chocolate and overall promotion of happiness, both to the consumers and the producers. Follow her on Twitter: @madelinecacao or her blog: www.cacaoycafe.org.  Picture credit: http://www.freedigitalphotos.net and Salvatore Vuono.

Man’s best friend?

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The idea that a dog is man’s best friend, and that children derive, not only enjoyment, but also valuable skills such as empathy and responsibility from owning a pet is so widely accepted in western societies that it has rarely been systematically investigated by researchers. Nevertheless, while some pet owners may well feel that their animal companions are a great comfort, or in some other way profoundly beneficial to them, others might view their pets as a nuisance, an unnecessary responsibility or expense, and even a source of stress.

While it may seem clear that pets are sometimes a profoundly positive influence on the lives of their owners, people vary enormously in terms of the quality of their relationships, human and animal alike, and the benefits derived from them. For that reason we need empirical research to determine how important pets really are to children, whether they are generally beneficial, and under what circumstances.

An evolving relationship
Humans and animals have a long history together. Cave paintings dating back over 30,000 years depict animals such as buffalo, horses, reindeer, wolves, and boars. For most of the Palaeolithic period, the relationships between humans and animals were ones of simple necessity; early humans competed for resources with animals, hunted them and were hunted by them. In the last 150,000 or so years, however, these relationships started to change with the domestication of animals for food, materials and labour. Early modern humans began relying increasingly upon, and spending more time alongside, animals, which were at the same time becoming evermore well suited to life with humans. Eventually, animals inevitably became providers of companionship and objects of affection to their human counterparts.

Today, pets are more common among North American and UK families with young children than are resident fathers. Nevertheless, their importance to children relative to other close relationships has received scant attention from researchers, as have the factors associated with the quality of child-pet relationships. This is in large part owing to a lack of valid tools for measuring human-animal relationships. I have endeavoured to redress these issues by examining the properties of a new pet attachment scale adapted from an established and psychometrically validated measure of human attachment.

Adversity
The results have supported not only the validity of this new tool, but also the validity of considering human-animal relationships in similar terms as human-human relationships in general. Having established its validity, this tool could then be used to see what factors were related to stronger relationships with pets, and also to compare children’s pet and sibling relationships.

Child-pet relationships were stronger among children struggling with various measures of adversity, including environmental adversity, emotional distress and academic difficulties. Nevertheless, stronger child-pet relationships were also associated with positive behavioural adjustment. This finding is striking given adversity is strongly associated with behavioural problems, in this sample and in general.

In terms of demonstrating the importance of children’s relationships with their pets, they were at least as strong as their relationships with their siblings, if not stronger. Moreover, children who suffered higher levels of adversity were more likely to prefer pets over siblings, indicating that not only do children turn to their pets for support when faced with adversity, but that they do so even more than they turn to their siblings.

Having demonstrated that children’s relationships with their pets are functionally similar to their relationships with their siblings, can be measured by the same instrument and are equally if not more important to them, many possibilities open up for further research in this burgeoning field. While more work certainly needs to be done, I hope that this research provides valuable groundwork for empirical studies of child-pet relationships.

*Matt Cassels [2014] is doing a PhD in Psychiatry. Picture credit: Witthaya Phonsawat and www.freedigitalphotos.net

 

Translating Africa’s tech enthusiasm into an enterprise ecosystem

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Technology is disseminating across Africa and technology consumer markets have grown rapidly as a result. But so far, only a few local technology entrepreneurs have seized the economic opportunities that ensue. In contrast to consumer markets, entrepreneurship ecosystems may take more time and resources to grow than enthusiasts of Africa’s technology boom anticipated.

Various media stories regularly celebrate the surges in mobile phone penetration, the distribution of laptops in rural schools and the steadily growing base of internet users, particularly in sub-Saharan Africa. For example, 10 years ago, less than 20 per cent of Africans owned a mobile phone; today, roughly 80 per cent do. The initial hype around Africa’s rapidly emerging technology markets was significant. Development and economic experts alike predicted that technology would allow local people to solve local problems and therefore drive innovation: rural farmers might access market information through feature phones and individuals in remote places could benefit from mobile healthcare and virtual education services. With technology consumer figures in East Africa growing at double digit rates every year, it seemed likely that the next big technology start-up would come out of Africa.

Multinationals profiting from tech boom

But now, a few years in, patience is starting to wane. Although technology is helping address local problems, the major start-up boom that angel investors and venture capitalists hoped for has not yet happened. Instead, the big economic opportunities of Africa’s technology catch-up are largely being seized by traditional multinationals. For instance, Kenya’s mobile service provider Safaricom, owned by Britain’s Vodafone, offers the mobile money service MPESA, which is returning million dollar profits across seven African nations. South Korea’s Samsung has a 50 per cent share in Africa’s overall smartphone market.

The reason is that, just like anywhere in the world, suddenly owning a mobile phone does not automatically make people relentless tinkerers and innovators. Instead, skilled developers, graphic designers and other technology experts tend to prefer stable employment to the start-up world. Given that unemployment rates are as high as 40 per cent in some African nations, this is not surprising. Add to that the risks associated with starting a business. Globally, an average nine out of 10 technology start-ups fail. Locally, starting a business tends to be even riskier: in the absence of personal savings and alternative employment options to fall back on, entrepreneurial success often becomes a matter of livelihood.

Forging a technology entrepreneurship ecosystem

One example of how to encourage entrepreneurs to seize the opportunities of Africa’s technology boom is through business incubation and acceleration. Across Africa, roughly 40 such organisations provide co-working and networking spaces, intensive business development programmes and sometimes seed funding. Although the basic parameters of African business incubators and accelerators are similar to those of their counterparts in Silicon Valley or London, their role couldn’t be more different. Instead of selectively fostering individual start-ups, Africa’s innovation hubs are driving the much more fundamental emergence of a technology entrepreneurship ecosystem.

For instance, innovation hubs are helping build technology skills by offering a space for collaboration. Before their existence, technology enthusiasts met irregularly in coffee shops or at universities. Now, there are dedicated spaces brimming with developers, graphic designers, hackers and bloggers every day. Business accelerators and incubators are also legitimising technology entrepreneurship as a profession, particularly in the eyes of parent generations. “Now you can actually say, I’m going to the hub. Before, it was like: I’m at the coffee house. It looked kind of like idleness,” a young technology entrepreneur explained to me. Finally, hubs’ seed funding for technology start-ups significantly reduces the financial risks associated with business creation or makes starting a business possible in the first place.

The question of how many vastly successful technology start-ups have come out of Africa might therefore not yet be one to ask. Instead, entrepreneurship takes more than the availability of technology. Although technology entrepreneurship ecosystems are emerging across Africa, often with the support of business incubators and accelerators, they are one example of how not everything can be leapfrogged.

*Marlen de la Chaux [2013] is doing a PhD in Management Studies.

Meeting global food demand through gene transfer

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The current exponential growth of human population places incredible demands on agriculture. It is estimated that agricultural production must double in order to meet projected demands by 2050. This increase must be made despite a steady loss of arable farmland, dwindling fertiliser reserves, increasing salinity of soils, limited irrigation water, climate change and shrinking of genetic variation in agronomic crops. Based on current agricultural increase, yield trends are inadequate to meet food demands by 2050.

Even now, about 870 million people are chronically undernourished. Over one billion people live on less than one pound per day and must spend over half of their income on food. Each year approximately eleven million children living in impoverishment die before reaching their fifth birthday and every day about 25,000 people die due to starvation related complications – making malnutrition one of the largest contributors to human mortality.

Inventive solutions

Meeting global food demands in the coming decades will require inventive and sustainable solutions. The scientific community agrees that one of the best ways to meet this demand for food is to enhance the ability of crops to harness energy from the sun.

Both food and biofuel production require photosynthesis to utilise abundant solar energy and store it in biomass via carbon fixation. However, photosynthesis is often limited by the availability of carbon dioxide. All plants use a photosynthetic mechanism known as C3 photosynthesis. Plants that use only C3 photosynthesis for the uptake of carbon dioxide are greatly hindered by oxygen, a waste product of photosynthesis. Interestingly, about 4% of plant species are able to overcome inhibition of oxygen and enhance their photosynthetic efficiency with a more efficient carbon fixation process, termed C4 photosynthesis, which acts as turbo charger to operate in parallel with the existing C3 pathway. In hot climates, C4 plants are more productive, drought tolerant and require less nitrogen than C3 plants.

Gene transfer

The specific objective of my research is to work towards comprehensively identifying the genes required for C4 photosynthesis with the goal to transfer them into economically important C3 crops, in particular rice and wheat which together account for about 40% of human food supply. Introducing C4 photosynthesis into these crops will potentially increase current yields by 50% while adding greater nitrogen- and water-use efficiency. If rice and wheat alone were to be converted to C4 and given the right environment, theoretically 1.4 billion more people can be fed per year without need for more farmland or agricultural inputs. This would be an incredible and sustainable solution to global food security and supply!

Transferring C4 photosynthesis into C3 crops involves alteration to leaf anatomy and partitioning the biochemical reactions encoded by existing C3 genes into different cell types, which facilitates more efficient carbon fixation. Thus, understanding how these photosynthesis genes are regulated paves a path to engineer more efficient crops for increased food and biofuel production. Transfer of C4 photosynthesis into important C3 crops could yield considerable gains by boosting world food supply at a time when agricultural production is predicted to drop beneath global demands.

*Gregory Reeves [2014] is a Plant Sciences PhD Candidate in the Department of Plant Sciences, University of Cambridge.