Organs-On-A-Chip: The Future of Drug Testing?

In 2006, six healthy men who participated in a seemingly harmless clinical trial for a new drug were instead left fighting for their lives with multiple organ failure. At Northwick Park Hospital in London, each had received an intravenous infusion of an antibody called TGN1412. German pharmaceutical company TeGenero initiated the first-in-human trial of TGN1412, developed to direct the immune system to fight cancer cells or reduce arthritis pain, after successful tests in animals.

Within 90 minutes of the infusion, all six developed a potentially fatal immune reaction with early symptoms like diarrhea, severe headache and vomiting. The volunteers became critically ill over the next 24 hours and were transferred to the intensive care unit. Episodes of respiratory and renal failure occurred in the following days, and they required mechanical ventilation, dialysis and plasma infusion.

Even though the men fortunately survived, the TGN1412 tragedy shocked the scientific world and revealed the true risks of human clinical trials. The infusion that brought them to the brink of death contained a dose 500 times less than the amount that had been safe in animal studies. In an investigative report, the United Kingdom’s Medicines and Healthcare Products Regulatory Agency failed to find any flaw in trial procedure or in manufacture of drug and concluded that the severe reactions were as a result of “unpredicted biological action of the drug in humans.”

The disastrous TGN1412 trial emphasizes the lack of physiologically relevant preclinical models that can predict human responses to new drugs. But what if an entire human lung, heart or kidney — or even the whole body — could be mimicked by a microchip for this sole purpose?

 

Researchers at the Massachusetts Institute of Technology have developed a microfluidic platform that connects engineered tissues from up to ten organs. Credit: Felice Frankel

Recent research has led to the development of what are called “organs-on-a-chip” (OOCs) to test the effects of drugs as an alternative to animal experiments, which may produce results inconsistent with human trials. These 3D microfluidic cell culture chips — about the size of a USB stick — are made of a translucent, flexible polymer lined with living human cells that can simulate the mechanics and microenvironment of an organ.

While initially developed to create computer chips, microscale engineering technologies like replica molding, soft lithography and microcontact printing allow researchers to manufacture these tiny model organs. The base material is polydimethylsiloxane, a biocompatible silicon-based organic polymer, which serves as a support for tissue attachment and organisation. From there, a biomaterial such as collagen acts as the extracellular matrix and scaffolding for the organ cells.

Since 2010, OOC models have been developed for the brain, lung, skeletal muscle, heart, skin, kidney, liver, gut and bone. But the goal for many laboratories is a full “human-on-a-chip” that would bring together several organs of the body for drug and therapeutic studies. Last year, a team of researchers announced the production of an integrated three-tissue OOC system comprised of liver, heart and lung. The resulting drug responses depended on interactions among the three tissue types, which reinforces the need to combine multiple tissue or organ types within a single microfluidic device. And earlier this year, engineers from the Massachusetts Institute of Technology created a microfluidic platform that connects engineered tissues from up to ten organ types.

Although the OOC remains an in vitro platform, it aims to replicate the in vivo environment of an organ with fabricated microwells, fluidic channels and porous membranes. It goes far beyond the conventional 2D cell culturing platforms, which feature a monolayer of cells to which a drug is then added. Such oversimplified models fail to capture the 3D cellular microenvironments in the human body, making it difficult to know how the drug will act once inside a person.

While some 3D cell culturing platforms have now been developed, such as cell aggregates and spheroids, they cannot capture any mechanical or electrical changes in cells. For instance, lung cells experience significant mechanical stress during inhalation, and the changes in surface-area-to-volume ratio that result play a critical role in gas exchange.

The first lung-on-a-chip, reported in 2010, had three embedded channels: two side channels and one main channel divided in half lengthwise by a membrane. The suction pressure within the two side channels could be controlled to stretch the centre membrane and mimic the mechanical stress during inhalation. Meanwhile, the porous membrane was seeded with cells to replicate the alveolar-capillary barrier in the lungs. In a toxicology experiment, the researchers added various nanoparticles to the alveolar microchannel and found that cyclical mechanical strain can accentuate the toxic and inflammatory response of the lung.

 

The placenta-on-a-chip, developed by a team at the University of Pennsylvania, contains two microfluidic channels that represent the maternal and fetal circulatory systems, and a membrane with living cells from the placental barrier that separates the two. Picture/Credit: University of Pennsylvania

 

Several laboratories have created hearts-on-a-chip to study different aspects of the cardiovascular system, such as the effects on drug delivery when stimulated with electrical and mechanical forces. A study that focused on liver-on-a-chip combined it with two other organ modules — uterus and breast — to test the toxicity of a chemotherapy drug after being metabolised by the liver. And a gut-on-a-chip has been developed to recreate the intestinal human environment in order to test the absorption of oral drugs. The applications for OOCs seem endless, as the field continues to expand and evolve. Lastly, a lab at the University of Pennsylvania recently made a placenta-on-a-chip to mimic the placental barrier between the maternal and fetal circulatory systems.

Then, of course, there are the practical advantages of OOCs such as saving on cost, time and labour. Spending on drug development over the last two decades has increased in the U.S., while the number of new drugs approved annually by the Food and Drug Administration has declined. Today, the cost of developing a new clinically applicable drug is nearly $2.5 billion U.S. dollars, and the drawn-out process itself takes 10 to 12 years on average. To curb the cost and time of drug development, some experts believe that OOCs could eliminate ineffective drug candidates as early in the process as possible.

While the research on OOCs continues to progress, much work is still required before a human-on-a-chip system becomes standard for drug development. Current models, even those that incorporate multiple tissue types, remain too simplified for researchers to rely heavily on. In the future, some experts foresee a modularised approach with libraries covering all levels and types of organs, and laboratories can then easily combine prebuilt modules for a specific application.

Reproducing Research Findings Comes at a Cost

 

The term ‘reproducibility crisis’ first appeared in a 2012 article which discussed the emerging problem of the lack of replicability of studies in the psychological sciences. The debate on the existence of such a reproducibility crisis and the question whether this applies only to some scientific fields is still ongoing. This clearly depends on both the nature of science and the methodology. If we take a step back and look at how the evidence for a scientific crisis is collected, we may find one of the issues that fosters the debate ad infinitum in the quantification of how widespread the phenomenon might be. A recent article suggests that if we measure the number of retractions or comments they do not seem to be booming extensively. This, as the author concludes, argues against the emergence of a reproducibility crisis and its influence on the scientific progress. Yet, the issue may simply not be completely verifiable. As Nobel Laureate Randy Schekman, who will participate in the panel discussion ‘Publish or Perish’ during the 68th Lindau Meeting, pointed out in his lecture at the 2017 Sackler Colloquia, the problem is evident in the fact that the information on replication studies lies mainly hidden within industries or research groups. Indeed, recent surveys among scientists show that incentives to publish reproducibility studies or, even more so, negative findings are low, and those who try to publish such studies are facing obstacles, with an estimate of only 10% of these ending up in a published article.

 

Scientific progress and research expenditure aside, we are looking at researchers who are rushing to get a tenured position somewhere. How much time will be spent on reproducibility studies? Indeed, some researchers suggest that reproducing previous findings is only worth the costs (in terms of time and money) in the case of very innovative ideas, and many more scientists estimate the time they spent trying to reproduce other researcher’s findings at around 30% of the total time they have available for research. If we consider 30% of a two-year fellowship, that amounts to 7.2 months  – this significantly affects the career progress of a scientist. Public institutions and funding bodies are increasingly considering the time since a PhD degree has been awarded when giving independent grants to individual researchers, and they continuously reduce the accepted timeframe. Does this particularly affect people who fail to build up on previous knowledge?

Surveys suggest that the great majority of researchers can either not reproduce their own findings or the ones from others. Unfortunately, not much data is available on the numbers of scientific studies that are reproducible, and the lack of an open communication on the subject among scientists – essential dialogue promoting scientific growth – is sometimes identified as one of the causes. Only 20% of researchers who participated in a survey by Nature were contacted because someone could not reproduce their work; the problem may be attributed to conflict avoidance or research secrecy.

 

The scientific career pyramid. Credit: Melania Zauri

One of the recent efforts to try to quantify the extent of irreproducible science in biomedical research is the ‘Reproducibility Project: Cancer Biology‘ which attempts to reproduce 50 cancer studies that were selected based on their high impact. The project is a collaboration between Science Exchange and the Center for Open Science and funded by the Arnold foundation. The analysis is carried out by researchers at specialised facilities and will, after peer review, be published in the journal eLife. The early data released is not comforting: only two of five reports analysed were fully reproducible. This number could be a crucial factor contributing to the disadvantage of researchers who cannot publish their work due to a lack of novelty, because they compete with those who have published high impact, yet often not reproducible, studies. If funding bodies took the time spent on reproducing findings into account, this could significantly improve the career selection system. Time spent on reproducibility studies should be included in the debate on the evaluation of scientists.

Indeed, in the whole scientific endeavour, progress, as Newton famously put it, comes with the ability to see further by standing on the shoulders of giants. No matter if the giants are big research groups, highly cited papers or any previous finding, we have to make sure that we can still safely stand on the shoulders of the large majority, if not all, of the published literature.

Networking at Conferences, or How to Win-Win at Lindau

 

There’s nothing like a good conference. I am a certified conference addict and I attend as many as I can each year. I love hearing the exciting presentations, meeting new people, gaining insight about new trends and innovations, and discovering novel ways to look at problems. From attending conferences, I have been able to move my career in new directions as I have met interesting people who have given me amazing advice and ideas.

I would have to say that my success – that is, the fact that I am in a career and job that brings me both joy and intellectual challenge – is a direct result of networking at conferences.  

And it should come as no surprise that one of my favourite conferences is my beloved Lindau (#NerdHeaven). It is hard to believe but the 68th Lindau Nobel Laureate Meeting (#LINO18) is about six weeks away. Did you know that this conference, which this year will be focused on physiology and medicine, will feature a staggering 40 laureates and 600 young scientists from across the globe? That is a lot of potential networking.

If you are planning to attend, you may be wondering how you can effectively leverage your time at Lindau to meet and greet as many people as you possibly can. But like many early-career professionals, you might also be new to networking and concerned that you might be overwhelmed by both the quantity and the quality of all the brilliant brains with whom you may come in contact.

Fear not, Fellow Nerd! I am here to help and ease your mind as you jump into this networking paradise. 

The first thing you should know about networking is that it is not a dishonourable activity, akin to selling a used car that is a piece of junk. In fact, networking is the exact opposite of this and is the most honourable action you can take in your career. The reason this is so is because networking is not about what can I take or get from you – rather, it is about what can I give to you, and what can I contribute to your team, organisation and project.

 

Young scientists during the 67th Lindau Meeting. Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Here’s a very simple and clear definition: Networking is a spectrum of activities that starts with the first point of contact I have with someone and aims for a mutually-beneficial alliance, where we are both providing value in various forms and functions over time. The win-win aspect of networking can last a lifetime, and is especially important, because when you look to offer something to someone in a networking partnership, you will find that hidden opportunities will be offered to you. Many of these opportunities are not necessarily measurable or even tangible (it could be something as simple as having a conversation with an established star in your field), but they can lead to critical career opportunities such as fellowships, jobs and awards. The key to networking is to endeavour to help the other party in some way over time. When you do this, they see you as honourable and are more likely to offer you tangible experiences which have the potential to be game-changers in your life and profession.

On 24 May 2018, I presented my second webinar in collaboration with the Lindau Nobel Laureate Meetings on “Optimising Your Time at Conferences: Networking Strategies to Advance Your Profession, Career and Field (Especially at Lindau!)”. Although Lindau was the focus of this webinar, I also discussed networking tactics that are applicable to any conference you will ever attend for the rest of your life. Talk about high ROI (Return on Investment)! (A video recording of the webinar is available in our mediatheque.)

 

  1. Know that everyone is there for the same reason. It helps to understand that everyone who attends Lindau (or any other conference) is there to network with everyone else. And at Lindau in particular, this goes for the laureates as well as the young scientists. I have interviewed more than a handful of Nobel Laureates who participate in Lindau year after year and have inquired why they attend and keep coming back. And over and over, their answer is the same – they want to meet and interact with other nerds, especially those who are just launching their careers. The Nobels know that networking is noble, so take a hint from them. And knowing that we all attend Lindau to network can help to ease your mind and relax. We are all in it together, and we all want to Network!

 

  1. Prepare. If you simply show up at a conference and participate in whatever events catch your fancy, you’re likely to miss the best networking opportunities. Before attending the conference, familiarise yourself with its programme. Start reading the programme now (or about a month in advance) and get to know the speakers and their backgrounds and the special events. This will help you make the most of the experience and arm you with intelligent questions to ask not only the laureates but the other young scientists as well.

 

  1. Plan ahead and make connections now. In general, it is fine to reach out to other attendees and even speakers who will be presenting at conferences. If you know you’d like to meet with fellow attendees, request appointments with them at least two to three weeks before the conference. They are busy, too, so it’s wise to get on their calendars beforehand. And even if the person you want to meet is not on the programme, it’s OK to reach out to ask if s/he will be attending, and, if so, whether her schedule would allow a short meeting. Ask for only 15 minutes, because most people attending conferences generally can’t afford to meet for a full hour for lunch, but they almost always can squeeze in a brief coffee appointment.

 

  1. Arrive early to talks and talk to those around you. Before coffee breaks are over, migrate back into the auditorium and sit near someone you don’t know. This is a great opportunity to network, especially for introverts, because there is a reason to speak with the other person: You are both here to attend the session and you can ask them if they have ever heard this presenter before. Furthermore, this networking has an expiration date and time – when the speaker begins their presentation, you have to stop talking immediately. This is a fantastic exit strategy and one that helps networking neophytes ease into networking because you can be completely certain that you won’t be stuck making conversation indefinitely.

 

  1. Tweet and use the conference app. Lindau has an especially robust and useful app that allows you to plan your schedule and get background information about the laureates and other participants (you will be notified once this year’s app is available for download). Most major conferences now use apps, and some even allow you to contact other participants through the app itself. Download the app before you leave home so you can make sure you know how to navigate it. And then once you are at Lindau, tweet away! The hashtag is #LINO18. Twitter is especially useful for conference networking because you can tweet and follow tweets with the conference hashtag. You’ll get incredibly useful insight about leaders, hot topics and popular sessions. Often, this information isn’t shared anywhere else. You’ll also discover who the trendsetters and other established leaders are in the community and get a sense for potential collaborators. You can retweet these individuals’ tweets to help establish and amplify your brand and demonstrate your dedication to the community. And by doing all of this, you’ll have a reason to contact your newfound colleagues after the conference.

 

  1. Look for “Action Nodes”. I define an action node as anything at a meeting that people can talk about, such as the queue for the food, drinks, registration and so forth. All of these nodes give you something to immediately discuss. For those who are unsure of what to say when you first meet someone, this can provide the spark.

 

I look forward to networking with you at Lindau and beyond!

 

Author’s Note: Excerpts and some of these concepts have appeared in other works by the author, including her book, Networking for Nerds (Wiley, 2015), career columns in Physics Today, Chemistry World, SPIE Professional, and NatureJobs, and other publications.

Fact-Checking – An Effective Weapon Against Misinformation?

 

Picture/Credit: Anne-Marie Miller/iStock.com

Starting out as a science writer, I fact-checked articles for a popular science magazine. Having pored over the text and checked each name, date and statement, it was satisfying to know that the reader would find facts, not fiction, on the pages. Invisible to the reader, this kind of fact-checking in journalism was used by TIME magazine and the New Yorker as early as the 1920s.

Today, anyone who reads the news is likely to have noticed another kind of fact-check: articles and media coverage examining the accuracy of reported claims or rumours, with politicians a common target. As independent checks, they are a way to tackle misinformation.

Fact-checking activity has increased dramatically within the last decade, long before the terms ‘fake news’ and ‘post-fact’ began popping up in headlines. In a recent census, there were 149 active projects in 53 countries. They include groups within the traditional media, like the BBC in the UK, and independent charities and NGOs like Germany’s Correct!v’s Echtjetzt. Not surprisingly, politics and economics dominate. A handful of projects, such as SciCheck and Détecteur de Rumeurs, are dedicated to science.

The rise of the fact-check is partly a response to the deluge of misinformation accompanying the internet and social media: never before could dubious claims be shared so easily, widely and quickly.

Fact-checking is also, however, a chance to document issues more thoroughly than in routine news reporting. An important goal of journalists is to cover all points of view to maintain impartiality. However this, along with increasingly under-resourced newsrooms and tight deadlines, can ironically result in false balance and misleading coverage. Coverage of climate change is a classic example.

“There’s been mounting pressure on journalists to call out false statements by politicians or by other interests in their reporting,” says Lucas Graves, a fact-checking researcher at the Reuters Institute for the Study of Journalism in the UK and former journalist.

Empowering the public to help them make political decisions is a high priority for many fact-checkers, as is improving public political discourse and making politicians more accountable.

There are many cases where fact-checks have forced politicians to change their rhetoric, says Graves. Last year, for example, the UK’s Channel 4 FactCheck forced Jeremy Hunt, then Secretary of State for Health, to correct parliamentary records after he stated 30,000 more mental health professionals had joined the National Health Service since his government took office. The true figure was 692.

One notable experimental study in the US even demonstrated that reminding politicians of the threat of a fact-check significantly reduced the number of negatively-rated fact-checks they received.

That said, such ‘wins’ are by no means universal. While there are reports that political parties do monitor fact-checks in the media, politicians don’t often acknowledge critical checks of their claims.

But how do the public respond to fact-checks? Overall, a huge body of literature on the subject suggests they have a modest corrective effect, says Graves. But it’s complicated.

First of all, a person must encounter a fact-check for it to have any effect: a significant stumbling block. To date, there hasn’t been much investigation into this. Exacerbating the issue are the media preferences of individuals with particular political beliefs. “People are much less likely to see, in the United States for instance, a fact-check of Donald Trump by PolitiFact if they’re watching Fox News,” comments Graves.

 

Fact-checking is booming. In the latest census, there were 149 active projects worldwide. Credit: Duke Reporters’ Lab

 

In any case, can we assume that once someone sees a fact-check, their misplaced beliefs are then corrected? This is the premise of the deficit model, a term coined by science communicators in the 1980s.

In reality, humans are more complex creatures with ideological beliefs, emotions and identities. Evidence on the benefits of vaccination, for example, is unlikely to persuade a parent with a strong distrust of conventional medicine to vaccinate their child against measles.

One particular phenomenon, confirmation bias, means that individuals favour information that aligns with their existing beliefs more readily than that which doesn’t. The anti-vaccine parent is therefore less receptive to information from vaccine proponents.

In a related phenomenon, the backfire effect, misplaced beliefs can even be reinforced. Demonstrated in a 2010 study, volunteers believed more strongly that there were weapons of mass destruction (WMDs) in Iraq in the run-up to the second Gulf War after they read an article describing how no such evidence was found.

Subsequent research, however, showed that the effect is rare and consequently less concerning for fact-checkers. Political scientists Ethan Porter and Thomas Wood studied the responses of individuals with a range of political beliefs to factual corrections of claims by politicians. “By and large, citizens heed factual information, even when such information challenges their ideological commitments,” they concluded.

The same study demonstrated, nevertheless, that individuals are happier to accept a correction of a claim that supports their beliefs, agreeing with previous research. Also, crucially, even if an individual accepts a politician has made a false claim, it does not mean they will change their beliefs on political policies. Likewise, a separate study has shown, they are unlikely to change their vote.

All in all, how society responds to fact-checking is nuanced and complex. Facts, so dear to scientists, are just one piece of the puzzle. One thing is clear, though: social sciences research is crucial to provide hard evidence on what works and what doesn’t. Equipped with this, fact-checkers can reach out most effectively, encouraging more constructive dialogue on the big issues that affect us all – including those involving science.

 

The Conversation is one of 149 organisations currently accredited by the International Fact-Checking Network. Conditions for accreditation include transparency in procedures, management and funding.

 

 

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CRISPR-Cas: The Holy Grail Within Pandora’s Box

Zur deutschen Version

 

“With great power comes great responsibility” – although most often attributed to the Marvel comic Spider-Man, this phrase has since become synonymous with new discoveries and techniques that harbour great potential but could also go terribly awry if not met with enough care. What might happen if the novel gene-editing tool CRISPR-Cas was employed without the greater good in mind, can be seen in the new Hollywood movie ‘Rampage’. This movie adaptation based on a video game portrays the disastrous, albeit not scientifically accurate, consequences of reckless gene editing, which results in the hero having to fight former friendly pet animals that have been turned into monsters with the help of CRISPR. Undoubtedly, CRISPR-Cas is one of the most ground-breaking scientific developments in recent years, but it is also still heavily debated among scientists and the public. So much so that even Hollywood took note.

But what exactly is CRISPR-Cas and how does it work? CRISPR (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are part of the bacterial “immune” system. Jennifer Doudna and Emmanuelle Charpentier, together with their postdocs Martin Jinek and Krzysztof Chylinski, developed the gene-editing tool, which uses RNA guide sequences specific to the target gene as well as the bacterial enzyme Cas9 to cut the target sequence out of the genome. If different Cas-enzymes accompany the RNA guide sequences, the system can also be programmed to insert or replace specific gene sequences. With these systems, researchers are able to permanently modify genes in most living cells and organisms. The break-through discovery was published in a Science paper in August 2012. The beauty of the technique: it is fast, cheap and relatively simple. As a consequence, the scientific community has seen a massive increase in CRISPR-related projects, papers and patents in the years since 2012.

In particular the medical research community adopted this new tool early on in the hope that precise DNA editing could eliminate genetic diseases and allow for targeted gene therapies to treat genetic causes of disease. In fact, recently, researchers managed to reduce the disease burden of such debilitating diseases as Huntington’s disease and muscular atrophy via targeted gene editing in mice. What is especially impressive about these first successful trials, is that the researchers have found a way to introduce the CRISPR-Cas system directly into the body. Previous approaches to improve immune therapies for certain cancers followed a different approach: blood or immune cells were isolated, their genetic code altered to better fight the tumour cells and then reintroduced to the body. For most tissues, however, this approach was not feasible. Thus, both guide RNA and enzyme had to be introduced directly into the body and aimed at their target tissue. However, both RNA and enzyme are large molecules, that don’t diffuse into cells easily and don’t survive well in blood. Therefore, some pharmaceutical companies have successfully started pairing the two components to fatty particles in order to facilitate their uptake into the cells. If these trials prove feasible, virtually any disease – from hepatitis B to high cholesterol – could potentially be eradicated by the CRISPR-Cas system.

 

Illustration of genetically modified lymphocytes attacking a cancer cell. Credit: man_at_mouse/iStock.com

 

Moreover, the CRISPR system not only proves tremendously useful for treating diseases, it is also being used as a promising new diagnostic tool: SHERLOCK – another pop-culture icon, but here the acronym stands for Specific High Sensitivity Reporter unLOCKing.

In 2017, a team of researchers in Boston first described an adapted CRISPR-system in which the guide sequence targets RNA (rather than DNA) as a rapid, inexpensive and highly sensitive diagnostic tool. The end product is a miniature paper test that visualizes the test result via a colourful band – similar to a pregnancy test. According to the scientists, SHERLOCK can detect viral and bacterial infections, find cancer mutations even at low frequencies, and could even detect subtle DNA sequence variations known as single nucleotide polymorphisms that are linked to a plethora of diseases.

In a new study, published earlier this year, the researchers used SHERLOCK to detect cell-free tumour DNA in blood samples from lung cancer patients. Moreover, their improved diagnostic tool is supposed to be able to detect and even distinguish between the Zika and the dengue virus.

The detection rather than editing of genetic information is based on the Cas13a enzyme, a CRISPR-associated protein, which can also be programmed to bind to a specific piece of RNA. Cas13 could even target viral genomes, genetic information underlying antibiotic resistance in bacteria or mutations that cause cancer. After Cas13 has cut its target, it will continue cutting additional strands of synthetic RNA, which are added to the test solution. Once these additional strands are cut by Cas13, they release a signalling molecule which finally leads to the visible band on the paper strip. The researchers have developed their diagnostic test to be able to analyse and indicate up to four different targets per test.

However, it is also this seemingly tireless activity of the cutting enzymes of the CRISPR toolbox that have led many researchers to question just how targeted and controlled this enzymatic reaction can be. In May 2017, a paper in Nature Methods reported a huge number of unexpected off-target effects, essentially labelling the gene-editing tool as unsafe. The paper brought the heated debate surrounding the predictability and safety of this new tool to the forefront of the field; however, in March 2018, the paper was retracted, after several researchers called the methods and in particular the controls of the first paper into question. The off-target effects observed earlier might have been due to different genetic backgrounds of the mice rather than the employed CRISPR-Cas method.

Nevertheless, many researchers caution their colleagues that the CRISPR-system and its possible side-effects are not yet fully understood. Another piece of the puzzle could be a natural off-switch for Cas9 that has been found in another bacterium and that could help control the enzymatic gene-editing system in the future.

However, possible side- or off-target effects are by no means the only fodder for heated debates surrounding the CRISPR tool box: in 2015, Chinese scientists reported that they had edited the genome of a human embryo. Although the embryo was not viable, it sparked a heated ethical discussion and conjured up many negative connotations regarding genetically engineered humans.

Leaving possible medical applications aside, CRISPR-Cas also holds great potential for agriculture. The gene-editing tool could help to generate plants that are resistant or at least more tolerant concerning fungi, insects or extreme weather phenomenon such as heat, drought or massive downpour, which occur more often in recent years due to climate change and can wreck entire harvests. The plants could also be made to produce higher yields or provide certain vitamins (e.g. golden rice), thus providing a huge relief in the fight against world hunger. However, the debate is still ongoing whether CRISPR-induced genetic modifications result in a genetically modified product (GMO) that should be labelled as such. GMO products are viewed critically by many customers and will thus be difficult to market.

The fact remains that the CRISPR-Cas system is a significant milestone in modern science with seemingly endless potential from diagnostic tests to curing nearly any disease there is, including a shortage of transplant organs, to alleviating world hunger. And yet, a system as complex and complicated as CRISPR-Cas needs to be met with due diligence and care in order to minimise risks and side effects. Moreover, the decision of altering the genetic code of (human) embryos requires in-depth ethical and moral deliberations.

 

 

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In Transition: Scientific Publishing in the Life Sciences

 

The history of scientific journals dates from 1665, when the French Journal des sçavans and the English Philosophical Transactions of the Royal Society first began systematically publishing research results. Over time, journals established conventions for publication that are intended to preserve the integrity of the scientific process (including an infrastructure for quality control and peer review) and they helped disseminate the scientific results. But they have come under increasing attack in recent years.

 

Nobel Laureate and eLife’s Editor-in-Chief Randy Schekman comments on today’s scientific publishing system:

“The assessment of scholarly achievement depends critically on the proper evaluation and publication of research work in scholarly journals. Investigators face a dizzying array of journal styles that include commercial, not-for-profit and academic society journals that are supported by a mix of subscription and page charges. The Open Access (OA) movement, launched in Britain but greatly expanded by the Public Library of Science (PLoS), seeks to eliminate the firewall that separates published work from public access. OA journals are funded by a mix of page charges and philanthropic or foundation support. Most OA journals embrace a more liberal licensing agreement on the use and reuse of published work, favoring the creative commons license rather than a copyright held by the publisher. Some publishers, particularly commercial firms, view the OA movement as a threat to the viability of their business plan. Major commercial publishers, particularly Elsevier, have fought against government mandates for OA publication of publicly funded research.

 

Randy W. Schekman during the 64th Lindau Meeting. Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

The most selective and successful journals, Science, Nature and Cell (a life science journal owned by Elsevier), maintain a firm hold on the high end of the scientific literature by appealing to investigators to submit only their most important work. Typically, these journals publish only a small fraction of the papers they receive and for the most part they rely on professional editors rather than active scholars to make key editorial decisions. In the past, publishers such as Nature and Elsevier, reinforced their high standing by relying on a metric, the journal impact factor (JIF) that computes the average number of citations of papers published in the journal during the preceding two-year period. As a consequence, many investigators, who quite naturally seek career advancement, strive to publish in these journals even at the expense of repeated cycles of review, wasteful additional experimental work and ultimately lost time. A growing number of investigators feel it is time for scholars to reassume authority for the publication of their research work and to eschew the use of JIF in the evaluation of scholarly achievement and favour OA publications over what I have called the ‘luxury’ journals.”

 

The major problems with scientific publishing are (1) the delay with which scientific results are published in journals, (2) the lack of transparency of the anonymous peer view process and (3) the usage of journal publications (in particular the Journal Impact Factor (JIF)) as the only recognised credential for researchers and the only path to career progression.

To improve and accelerate science without any compromise on quality, reforms are needed:

  1. Scientists should be able to put their academic papers, along with experimental data, in publicly accessible “repositories” (e.g. preprint servers like BioRxiv) before they are sent to a journal. That would allow other researchers to make use of the findings without delay.
  2. Journals should implement open peer review.
  3. A new metric should be implemented to measure the impact of the work of scientists (e.g. the Relative Citation Ratio).

ASAPBio – a scientist-driven initiative to promote the productive use of preprints in the life sciences – is doing a tremendous job to drive these reforms. This initiative not only organises meetings and workshops to gather major stakeholders, but it also acts as an information hub for the life sciences community (tracking of journal, funder, and university policies).

 

Preprint journal clubs – A way to support the preprint movement

Although preprinting becomes more and more popular in the life sciences, only 1% of papers are uploaded to all preprint servers so far. Great ways to help the movement gain momentum (besides publishing your work in a preprint journal) are by citing and commenting on preprints and by reviewing a manuscript in a preprint journal club. A preprint journal club can provide early feedback during the preparation of a scientific manuscript and it is furthermore a more meaningful review experience.

 

Nobel Laureate Martin Chalfie is an advocate of preprint journals clubs:

 

Martin Chalfie at the 67th Lindau Nobel Laureate Meeting. Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

For the last year my lab has had a journal club every other week with papers taken from bioRxiv.org, i.e., unpublished preprints.  The idea to have such journal clubs came from Francis Collins.  We usually find a manuscript of direct interest to the lab every time we search the archive.  After we have discussed the paper, the person leading the discussion collects our ideas and suggestions and conveys them to the authors.  We do not post our evaluations with the paper on bioRxiv but prefer to let the authors consider them privately. The advantages of a preprint journal club over a journal club reviewing published papers are 1) lab members read the latest material (often posted within the previous week or two), 2) they feel that reviewing a paper is not an empty exercise (because the paper is already published), but something that actually helps people, 3) they learn about improving manuscripts, and 4) authors get more feedback.   I also email people and suggest they similarly discuss our papers when we submit a manuscript to the archive, which, for us, is when we submit the paper to a journal.  So far, everyone (members of the lab as well as the authors of the papers we discuss) have enjoyed the exercise, and many of the authors we have written to have said they intend to start their own preprint journal clubs.  I hope others will also set up similar preprint journal clubs not only for the individual benefits, but also the real benefit of building a more sharing scientific community. After all, we are in this together.”

 

Without doubt we live in exciting times, and we should embrace these changes and even help them along, because open and transparent science is better science for everyone!

 


 

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What Your Advisor Didn’t Tell You: You’re a Super Hero and You’ve Got Yottatons of Skills

Photo/Credit: Julia Nimke/Lindau Nobel Laureate Meetings

 

When you were studying for your degree, did your mentor or principal investigator (PI) ever happen to mention to you: “Good news! Not only are you developing technical skills in science and engineering, but you are also honing vital and transferrable skills in other realms, too!” No? I didn’t think so.

As a maths major, I certainly didn’t hear that from my advisor. In fact, I was led to believe that the only skills I had were tied to maths and the only job and career I was qualified for had to have the word “mathematics” in the title – as in, mathematician, maths professor, maths teacher, and so forth.

What a silly idea.

Your degree may say “chemistry”, “physics” or “pharmacotoxicology”, but hidden below the surface of your disciplinary expertise is a truckload of highly vital, attractive, invaluable, and diverse skills. These skills fan out across multiple dimensions and encompass much more than your scientific knowhow. In fact, these skills are highly coveted by many more sectors and ecosystems of which you and your PI might not have been aware. They include hard business skills and “soft” or interpersonal skills, such as communications, negotiations, conflict resolution, marketing, and leadership.

Because our advisors typically have not spent time outside of academia, they often do not realise that they, too, have these skills. But more importantly, they don’t think to inform their proteges that they possess these abilities and that the proteges can and should specifically articulate that they have them when looking for jobs and planning out their career paths.

Let’s take a look at the origin story of these skills. From studying science or engineering and, in particular, pursuing it at the graduate level and beyond, you have organically gained certain critical problem-solving skills. You have been bestowed these super powers through the process of conducting scientific research, in which you have to identify a problem that is not possibly known to exist and identify a solution from nothing. You are creating knowledge and/or developing an innovation. This is not something to take lightly, as this serves as the foundation for your entire brand (your promise of value) to employers because this is what employers desire – they need Creators and Explorers, who can solve problems that at first glance seem impossible. Scientists and engineers are trained to think in the direction of the impossible, to create something from nothing, to find and explore and measure realms that are unseen and unknown.

 

In your pursuit of the unidentified and unfamiliar, you have developed certain attributes that serve you well in your day-to-day super hero business of STEM. For example, you:

  • Are adaptive, adaptable and flexible
  • Take a critical thinking and analysis approach
  • Are very self-disciplined
  • Have excellent computing skills
  • Can solve a problem from the ground up
  • Are both holistic and detail-oriented
  • Understand how the physical world works
  • Have extensive project management and teamwork experience (after all, your teams are often large-scale, diverse and across continents and cultures)
  • Have networking experience, from finding and working with collaborators

 

You also have a considerable amount of business skills. I am sure your advisor never hinted at this aspect of your glory either, partly because they probably didn’t realise themselves that they have and use hard business skills on a regular basis every day in their research. For example, did you know that you and your mentor have marketing experience? When you pen a grant proposal, you are essentially writing part of a marketing campaign. You are suggesting to the agency or organisation that they invest in you and your research and you outline why this will be a good investment and how the financier will obtain a return on their investment. That is Marketing 101: explain to the customer why they should buy your product. In this case, the product is your research and the impact you will have, and the customer is the funding agency.

 

There are plenty of other hard business skills that you probably gained from engaging in STEM, such as:

  • Project Management
  • Accounting
  • Human Resources and Training
  • Procurement and Inventory
  • Risk Management
  • Customer Service
  • Sales and Marketing
  • Public and Media Relations
  • Event Planning
  • Grant Writing
  • Operations
  • Vendor Relations
  • Supply Chain Management
  • Standard Operating Procedures (SOPs) and Safety Protocols
  • Quality Assurance

 

As you talk with your advisor and others within academia, it is relevant to note that these skills are probably being described using a different vocabulary. I noticed this myself when I was working for a university and looking to get a job beyond the academy. On my resume, I described the problems I had solved in terms of students, i.e., what I had done to advance students’ goals and recruit more students to the institution. I wasn’t getting any interviews. And then, thanks to a career counsellor, I changed one word on my resume and suddenly I got many interviews. What did I do? I simply swapped out the word “student” for the word “customer”, because if you think about it, what are students to a university? They are the customers of academia – they exchange money (their tuition) for a product and service (their degree and the education that comes with it). Once I communicated that I spoke the language of industry, and articulated my skills using their vocabulary, they were more inclined to interview (and hire!) me.

So how do you start identifying your own set of skills? Use a tool I have created, called the Skill Inventory Matrix.

This is a self-assessment tool that you can utilise to not only recognise the skills you have acquired, but also to analyse and determine what opportunities are good for you to explore and pursue given your goals, interests and skills. Before you begin to complete it, know this: this is a private document. You won’t ever need to show this to anyone. It is a personal tool designed to help you articulate your true value which you can use to populate your resume or CV, cover letters, introductory emails, profiles on LinkedIn and other social media sites, and any other self-marketing document and communique, throughout your career. So be truthful, thoughtful and thorough as you endeavour to fill it out, because it will provide you with extremely powerful information about your skills and value that will arm you to make the right career choices for you and only you.

It is also a living document: the more experiences you have, the more projects you complete, the more jobs or assignments or gigs you pursue, the more information you can glean about yourself. So keep this tool handy throughout your entire career so that as you have accomplishments you can add to it to be able to more methodically and authentically tell your own value story.

The Skill Inventory Matrix

 

In the first column, list out any experience that literally gave you experience, which could be a paid job or research assistantship, or a volunteer position, or a short-term class project.

Then in the next columns, write down what different types of skills you gained from each experience. As you fill this out, don’t worry about spelling or even vocabulary – if you don’t know the precise word for it, describe the skill in terms of the problem you solved.

In the “characteristics” column, jot down what you realised about yourself from this experience, such as you work well in a team or independently, or you thrive when given a deadline.

And finally write down what you loved and hated about these experiences. This is useful data to have to plan out your career – we will cover this in a future blog so stay tuned!

In the meantime, as you start filling in your Skill Inventory Matrix you will discover the full extent of your value and the plethora and diversity of skills you have. And then you will know what I mean when I call you a super hero. Because that’s what you are.

 

Author’s Note: Excerpts and some of these concepts have appeared in other works by the author, including her book, Networking for Nerds (Wiley, 2015), career columns in Physics Today and Nature Astronomy, and other publications.

 

 

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Science Should Prepare for a Marathon

Science can no longer be complacent about its role in society. Global inequality and dissatisfaction with the global financial system that is perceived to perpetuate this inequality has led many into the arms of populists. In a highly polarised environment, it is not only political and financial mechanisms that are being called into question, but also scientific facts. A ‘post-truth era’ has arrived in which scientific evidence is no longer necessarily perceived as the gold standard. Last year, it wasn’t only the scientific enterprise in general that was beleaguered: the institutions of science and learning and scientists themselves also came under attack in numerous places around the globe, from Hungary to Turkey

These tempests have acted as a jolt that has awakened the scientific community and supporters of science into action. Many scientists now acknowledge that they must invest more time and effort in communicating not only scientific results but also the nature of scientific investigation to the public. Huge numbers, provoked in particular by the politics of US president Donald Trump, also felt moved to take a visible stance in support of science. A worldwide March for Science took place on 22 April 2017, in which people from more than 600 cities around the world took to the streets. This year, supporters all over the world will march again on 14 April 2018. A prominent supporter of this initiative is Helga Nowotny, Vice-President of the Council for the Lindau Nobel Laureate Meetings and former President of the European Research Council. Nowotny was the first signatory of the Vienna March for Science, and gave the closing speech at the event in 2017. 

 

More than 2000 people participated in the Vienna March for Science on 22 April 2017. Photo: © March for Science Vienna

More than 2000 people participated in the Vienna March for Science on 22 April 2017. Photo: © March for Science Vienna

Why have you given your support to the March for Science?

Helga Nowotny: For a long time, it has been said that science has facts and society deals with values. It is finally time to abolish this separation – it no longer applies! Because science is also based on values. One of these values is the freedom to ask questions and to step into the unknown. At the same time, facts don’t fall from the sky, but are the result of a long process of scientific investigation. As scientists, we need to better convey how we arrive at facts. We should have more confidence in people’s power of judgement, whilst also helping them to acquire this power. This is necessary if we want to transform information into knowledge.

 

Do scientists then need to communicate more? Has their reticence contributed to the current situation?

HN: Of course, one can always communicate more. However, I would like to stress that science cannot be isolated from what is happening in society, and when politicians push science to the side or try to instrumentalise it, then this creates space for populists of all kinds. The scientific community needs to understand that it cannot fully insulate itself from political events, because it is part of society. It is important to realise that science is not the primary target of ‘alternative facts’. However, it is confronted with considerable collateral damage. Around 2,000 people participated in the Vienna March for Science. In total, an estimated 1.1 million people worldwide took to the streets in support of science on 22 April 2017.

 

The initiative for a March for Science came about as a direct reaction to the politics of US President Trump. Why have people now in parallel also taken to the streets in Vienna or Munich?

HN: It is important to stress that this was a march FOR science and was not a march against something. Of course, the current political situation in the USA played a subliminal role, but the march cannot be reduced to an anti-Trump demonstration. Rather, the intention was to raise the profile of science. A post-truth mentality appears to be characteristic of these troubled times.

 

 

Helga Nowotny was speaking as a panellist at a press talk on 'Science in a Post-Truth Era' during the 67th Lindau Meeting. Credit: Julia Nimke/Lindau Nobel Laureate Meetings

Helga Nowotny during a press talk on ‘Science in a Post-Truth Era’ at the 67th Lindau Meeting. Credit: Julia Nimke/Lindau Nobel Laureate Meetings

What dangers does it pose?

HN: Above all, through the constantly changing positions of US president Trump, we can see how unstable and volatile the geopolitical situation has become. This has effects worldwide. One element of the post-truth mentality is the irresponsible handling of solid findings. Such an attitude is particularly dangerous at present due to the enormous problems that we face, not least climate change.

 

Is the current situation unique in history?

HN: What is unique is the strong entanglement with economic processes. The pursuit of economic growth is, as before, a driving force in society, and from the point of view of politicians, science and technology are the engines of this growth. The great progress that has been made, for example, in smart technologies, is quite remarkable, but we need to address the problem of the jobs that are being lost in this way.

 

Where do things go from here after the March for Science? Are you optimistic this current movement will change anything?

HN: This is the beginning of a process. I think all who took part in the March for Science agreed on that point. As the Vienna City Marathon took place the day after the march, I would like to use it as a metaphor. One march won’t do it: Science should prepare for a marathon!

 

 

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A Once-In-A-Lifetime Experience

View of Lindau Island from the zeppelin. Photo/Credit: Laura Schönhardt/Lindau Nobel Laureate Meetings

There is a distinct lack of conversation about the Lindau Nobel Laureate Meeting in South Africa – the first that I heard of this opportunity was when I was asked by my supervisor if he could nominate me to attend the 67th Lindau Meeting. The selection process is very rigorous, and it was 4 months after submitting my application that I received an email informing me that I had been selected to attend. I was extremely excited to receive this email, to the point that I immediately rushed to my supervisor’s office to tell him the news. A travel grant was provided by ASSAf, and as the selected delegates were from different universities and research organisations throughout South Africa, ASSAf organised a pre-meeting team-building gathering, during which we met the other delegates. Several Lindau alumni were also invited to this gathering, to share their experiences and give us advice on how we should approach the meeting. This advice varied from the sensible, ‘Meet as many people as you can’, to the less sensible, ‘Don’t sleep at all’. For my stay, I was hosted by Lindau residents, and my host family proved to be exceptional. They went so far as to organise transport for me from Munich to Lindau, and to make sure that I got onto the correct train at the end of my stay. We had many discussions, which varied from the nuances of our cultural differences, to discussions about topics raised at the meeting, to sports, politics, and everything in between. The experience of being hosted by locals added substantially to the entire ‘Lindau experience’.

During the meeting, numerous programme additions were organised, to which only a small group of researchers was invited. These additions were sponsored by research organisations or multinational corporations. I was fortunate enough to be invited to attend two such events. The first event was the Summer Festival of Science, which was hosted by the German Federal Ministry for Education and Research. During this event, I found myself conversing with CEOs and vice-presidents from large multinational companies such as the Linde Group, Cabot Corporation and Lockheed Martin. Another opportunity was a flight in a zeppelin, as a part of an introduction to the ‘Clockwork Ocean’ expedition being undertaken by the ‘Helmholtz Zentrum Geesthacht’ of the Helmholtz Association. We were introduced to the methodology and equipment used to study the behaviour and impact of water eddies in the seas and oceans. Thereafter, we were taken on a 45-minute flight in the zeppelin for a magical view of Lindau and the Bodensee from the sky. We were joined for this flight by two Nobel Laureates, who were just as enthralled as we were by the views that unfolded.

 

On board of the zeppelin, expedition director Burkard Baschek from Helmholtz-Zentrum Geesthacht explains the research of ‘Clockwork Ocean’ to Mark Williams-Wynn, Nobel Laureate Dan Shechtman and others. Photo/Credit: Roland Koch/Helmholtz-Gemeinschaft

 

The days of the conference flew past at a breath-taking pace, although not without presenting each of us with many opportunities to network and to learn from both the Nobel Laureates and the other researchers present. The advice from the alumni to not sleep made much more sense at this point. There were simply so many interesting people to meet and to discuss science with, that we all ended up sleeping far less than usual. For me, the lectures that most stood out were those in which the Nobel Laureates chose to share their personal experiences as researchers. These were lectures by Peter Agre, Dan Shechtman (2011 Chemistry Nobel Laureate) and Martin Chalfie (2008 Chemistry Nobel Laureate). After the lectures, each Nobel Laureate held a discussion session with the young researchers. I found Shechtman’s discussion session particularly pertinent to me, as we discussed science entrepreneurship and education. There was a strong emphasis on women in science, technology, engineering and mathematics (STEM) at this year’s meeting, and as such, many of the young scientists involved in discussion panels and sessions were women. In stark contrast, only one of the 29 Nobel Laureates present was a woman (Ada Yonath, 2009 Chemistry Nobel Laureate).

On the final day of the meeting, we were treated to a boat ride to the garden island of Mainau, where we spent the day. Two occurrences during the events held on the island further highlighted women in STEM. During the closing panel discussion on ‘Ethics in Science’, a young researcher from the University of Cambridge, Dr Karen Stroobants, was, by far, the stand-out panel member, eclipsing the otherwise male-dominated panel. Secondly, Dr Hlamulo Makelane, from South Africa, gave heartfelt and emotive closing remarks for the Lindau Meeting on behalf of the young researchers, doing South Africa and women in STEM proud. Everything considered, the Lindau Nobel Laureate Meeting was a once-in-a-lifetime experience that I would recommend to anyone who is eligible to attend. Were it not for the fact that young scientists are only afforded the opportunity to attend once, I would have applied immediately for the next meeting.

 

This article is an excerpt from “Young South African researchers attend the 2017 Lindau Nobel Laureate Meeting” by Nolwazi Nombona, Mark Williams-Wynn and Paul Kennedy, which was originally published in the South African Journal of Science.

“The Networks Created Will Benefit My Scientific Research Career for Years to Come”

Nolwazi Nombona at the African Outreach Breakfast during the 67th Lindau Meeting. Photo/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

 

The first that I heard of the Lindau Nobel Laureate Meetings was when a senior professor approached me to ask if they could nominate me to attend. I secretly thought: Why would they select me? But I submitted an application and then promptly forgot about it. Months later, I received an email that turned my world on its head. The African Academy of Sciences had nominated me for consideration to the Council and I was chosen to attend. I couldn’t believe it: I was going to Lindau! I was excited for the opportunity to meet and interact with Nobel Laureates – the remarkable people I’d only read about on the Internet. But after the initial elation, the nervousness kicked in. I worried to myself: What on earth would I possibly have to say to them? In hindsight, my fears were completely groundless.

My experience far exceeded any of my expectations. The atmosphere in Lindau was friendly and relaxed; and this made the interaction with the Nobel Laureates far less intimidating than I had expected. At the opening ceremony, the excitement in the auditorium was tangible. As became typical for the duration of the Meeting, we had an opportunity to mingle with and meet the Nobel Laureates as well as fellow researchers who hailed from all corners of the globe. The Meeting was centred on lectures, discussion sessions, and science breakfasts, but outside of these times, there were many opportunities to discuss topics ranging from current research activities to politics and cultural norms. Over the course of the week, the Nobel Laureates delivered short lectures; some focused on the fundamental challenges in their respective research areas, whilst others shared their experiences as researchers. For me, the highlight was the keynote address that was delivered by Prof. William E. Moerner (2014 Chemistry Nobel Laureate) on behalf of Prof. Steven Chu (1997 Physics Nobel Laureate). Chu mentioned that governments seem to be in doubt about scientific evidence (especially on climate change) and emphasised the need to have political scientists who can work with governments to develop better policy options for a sustainable future. Apart from the scientific aspects that were covered during the lectures, what was of most value to me was the guidance that each Nobel Laureate imparted during their lecture. They motivated us to never doubt our abilities and inspired us to hold on to the passion we have for science. Possibly the most interesting lecture (judging from the applause given) was delivered by Prof. Ben Feringa (2016 Chemistry Nobel Laureate). In his talk, Feringa took us through his discovery of a ‘nano-car’ which he built from compounds that use light-induced chemical energy to move across a surface, highlighting the positive impact these nano-machines could have, especially in medicine.

The African delegates had a special African breakfast with Prof. Peter Agre (2003 Chemistry Nobel Laureate). This breakfast gave us a chance to meet other African delegates and we had a rare opportunity to pick Agre’s brain regarding his work in Africa through his role as the Director of the Johns Hopkins Malaria Research Institute. The discussion touched on various issues, including why we have not been successful in eradicating malaria. The dialogue was so thought-provoking that ASSAf organised a follow-up lunch discussion with Agre and the researchers from South Africa. The Lindau Nobel Laureate Meeting was a unique experience, and it exposed me to colleagues working on similar research projects around the world. The discussions were enlightening, and the networks created will benefit my scientific research career for years to come. I would encourage every young scientist to apply to attend this meeting, as it provides a remarkable opportunity to interact with current and future Nobel Prize winning scientists from across the globe.

 

This article is an excerpt from “Young South African researchers attend the 2017 Lindau Nobel Laureate Meeting” by Nolwazi Nombona, Mark Williams-Wynn and Paul Kennedy, which was originally published in the South African Journal of Science.