28th Jan 2021
The University of Pretoria (UP) has discovered new potent chemical compounds that show potential as candidates for both the treatment and elimination of malaria.
Professor Lyn-Marie Birkholtz, Professor in Biochemistry and South African Research Chair in Sustainable Malaria Control (part of the South African Research Chair Initiative, SARChI), was part of an international team that published this discovery in the journal Nature Communications on 11 January. “The breakthrough involves the identification of unique compounds that are able to kill several stages of the malaria-causing parasite and can block the transmission of the parasite between humans and mosquitoes,” she explained.
The deadly human malaria parasite Plasmodium falciparum occurs in South Africa. These parasites are transmitted to humans by female Anopheles mosquitoes. The only means of killing the parasite itself is to use chemical drugs, but new antimalarial drugs are urgently needed to address the growing concern of antimalarial drug resistance.
Prof Birkholtz describes the parasite as a “shape shifter” since it can take on multiple forms while in humans. Some of the forms cause disease and others allow the parasite to be transmitted back to mosquitoes to continue the life cycle. Prof Birkholtz states: “To eliminate malaria, it is essential that we have the necessary tools to kill all these different forms of the parasite. We can then cure patients of the disease but, importantly, also block the malaria transmission cycle. This is the only way to achieve malaria elimination.
South Africa is leading regional malaria elimination efforts as part of four frontline countries in southern Africa including Namibia, Botswana and Eswatini.
In an innovative strategy, the team looked for new chemical compounds that can do exactly this, but that are completely new so that the parasite does not have resistance against them. The team runs a unique research platform on the African continent, in which all of these stages of the malaria parasite can be produced in the lab and be used to test chemical compounds. The team discovered compounds that kill the disease-causing form and compounds that blocked the parasite from infecting mosquitoes in the lab.
Two potent compounds target processes essential to the parasite’s survival: one is a clinical candidate against tuberculosis and blocks cell membrane synthesis and another is an anti-cancer candidate that targets epigenetic mechanisms (mechanisms that control cell fate beyond the genome). “This is the first time that these compounds were shown to have activity against malaria parasites and since they are not toxic to humans, they show the potential to be developed as antimalarials for both the treatment and elimination of the disease,” said Prof Birkholtz.
The discovery was made possible by the team’s use of an open-source chemical compound set called the Pandemic Response Box, developed by the Switzerland-based Medicines for Malaria Venture (MMV) and the Drugs for Neglected Diseases Initiative (DNDi). This compound box contains compounds that can be used for drug repurposing/repositioning, a process where drugs that have activity against a specific disease (e.g. cancer) can be reused for another disease (e.g. malaria). Dr James Duffy, MMV Project Director, describes the discovery “as an important breakthrough that emphasises the potential to use existing drugs as inspiration for drug discovery projects targeting different diseases. Never before has this been more important than in light of current outbreaks, where the rapid response to discover new chemicals able to kill infectious organisms is essential.”
Prof Birkholtz directs the parasite cluster of the UP Institute for Sustainable Malaria Control (ISMC), a multidisciplinary institute with a focus on integrated innovations towards malaria elimination in South Africa. Professor Tiaan de Jager, Director of the ISMC and Dean of Health Sciences at UP, said: “A discovery of this kind attests to the leading expertise in antimalarial drug discovery at UP, and in South Africa, addressing African-centred societal challenges. This work also shows the commitment of scientists at UP to contribute to the United Nation’s Sustainable Development Goal for Good Health and Wellbeing.”
Prof Birkholtz’s team led the transmission-blocking drug discovery effort as partner in the South African Malaria Drug Discovery Consortium (SAMDD) that includes two other South African Research Chairs, Professor Kelly Chibale (Chair in Drug Discovery at the Drug Discovery and Development Centre, H3D, at the University of Cape Town) and Professor Lizette Koekemoer (Chair in Medical Entomology at the WITS Institute for Research on Malaria at the University of the Witwatersrand) as well as scientists from the Council for Scientific and Industrial Research and international partners from the USA and Spain. The work has benefitted from sustained funding from the MMV and the Medical Research Council’s Strategic Health Innovation Programme (SHIP) and affirms that investments in health innovations places South Africa at the forefront of discovery.
Story by: The University of Pretoria
15th Jan 2021
Ever since the virus now known as SARS-CoV-2 was first identified and sequenced by researchers in China a year ago, a tidal wave of research on the pathogen and its associated disease, COVID-19, has swamped the scientific literature. Indeed, an analysis posted as a preprint last month found that more than 84,000 papers related to COVID-19 were published in the first 11 months of 2020.
Even given that output and the recent rollout of vaccines against the disease, researchers who study the virus aren’t ready to put it on ice and move on to other problems. Here are some of the key areas where we’re likely to see advances in understanding this year.
Where did it come from?
Teasing out SARS-CoV-2’s origin is important, says disease ecologist Jonathan Epstein of EcoHealth Alliance, because knowing how the virus got into humans could yield clues about how to avoid future spillovers. The SARS outbreaks of 2003 and 2004 spurred research (of which Epstein was a part) that identified horseshoe bats as a reservoir for this family of coronaviruses, he notes, but it’s still not known exactly how either virus made it from bats to people. Understanding whether SARS-CoV-2 jumped directly from bats into people, or whether it first infected a wild or domesticated intermediary species, would help in pinpointing particular human activities that could be putting us at risk of future zoonotic events, he says.
The World Health Organization (WHO) has convenened a team to investigate the virus’s origins that began traveling to China early this month, WHO head Tedros Adhanom Ghebreyesus said in a January 5 briefing. According to WHO spokesperson Tarik Jašarević, the team’s plans include reviewing hospital records from late 2019 to identify illnesses that might have been COVID-19, interviewing people who were the first known cases, and finding out what animals were traded at a market in Wuhan associated with some early infections, and possibly other local markets around the time of the outbreak, and where those animals came from. Jašarević did not say when the team’s findings might be made available.
In addition to prevention, another benefit of knowing the animal origins of coronaviruses is the opportunity to design medicines against them in advance, namely, “broadly neutralizing antibodies that can hit not just SARS-2, but other related coronaviruses that we know are in animal reservoirs,” says virologist Kartik Chandran of Albert Einstein College of Medicine in New York. That’s a long-term goal of his current work on identifying effective antibodies that can be used as a COVID-19 drug. And, he says, it will also be important to figure out how to develop vaccines that confer protection against a broad swath of such coronaviruses. “From a research standpoint, in the next few years, that’s going to be a major challenge.”
More treatment options
Even with effective vaccines, humanity is likely stuck with SARS-CoV-2, much like the cold-causing coronaviruses and influenza, Chandran says. That means there’s an ongoing need for effective treatments for the disease. One issue with current monoclonal antibody treatments, he notes, is that they require large volumes to be administered by IV, creating logistical challenges. “If we can get these things to be potent enough, we ideally would be able to give them by intramuscular injection, rather than giving them IV—that would make a huge difference,” he says. “But that’s going to require a jump in potency that’s quite significant.”
So far, one standalone monoclonal antibody, bamlanivimab, and a combination of two, casirivimab and imdevimab, have received emergency use authorization from the US Food and Drug Administration (FDA). Both treatments were tested in clinical trials on people with mild or moderate disease, and the studies found that those who received them had about one-third the risk of visiting the ER or being hospitalized in the following four weeks compared with patients who got a placebo. Other currently available treatments include the antiviral remdesivir and the steroid dexamethasone, each of which are used for some hospitalized patients, and convalescent plasma, which, according to a small trial published this week, halved the risk of severe respiratory illness when given within three days of the onset of symptoms.
“We were encouraged to see the quick pace of development of the monoclonal antibodies,” says Esther Krofah, the executive director of the FasterCures center at the nonprofit Milken Institute. “But I think there’s still a lot more to be done, particularly in an outpatient setting.” In particular, a small-molecule drug that could be taken by patients at home to reduce their chances of hospitalization would alleviate some of the pressure on the healthcare system. One such drug she’s keeping an eye on, camostat mesilate, is a protease inhibitor currently being tested in multiple clinical trials.
FasterCures is tracking more than 300 prospective vaccines and treatments for COVID-19 that are in various stages of development. Krofah says she expects many current clinical trials not to yield conclusive results due to poor design or problems recruiting enough patients. One promising tack, she says, are the so-called master protocol studies that compare different treatments both with each other and with a placebo.
A series of such trials sponsored by the National Institutes of Health, for example, several of which are expected to be completed later this year, are testing immune modulators, monoclonal antibodies, and blood thinners in groups of COVID-19 patients. In other trials, some repurposed antibiotics and an antifungal have also shown promise and could make it to the clinic this year, says Yasmeen Long, also of FasterCures.
As SARS-CoV-2 continues to mutate, researchers will need to determine whether available vaccines are effective against newer variants, Chandran says, such as the B.1.1.7 and 501.V2 variants that have drawn much attention in recent weeks. Akiko Iwasaki, an immunologist at Yale University, says that while current variants are “likely going to be covered by the existing vaccines, in the future, there may be new variants that can emerge that would evade the current vaccine”—meaning surveillance of viral variants should be a priority.
To date, the US has sequenced 58,560 SARS-CoV-2 samples, compared to the UK’s 209,038, The New York Times reports, but a Centers for Disease Control and Prevention official tells CNN that the agency and its partners are working to double the number of viral sequences they post publicly each week to about 6,500.
The long haul
One of Iwasaki’s current projects is profiling the immune responses of people whose COVID-19 symptoms have lasted for months, a phenomenon known as long COVID. “Right now, there are thousands of people suffering from long COVID,” she says. “But there’s very little insight as to how the disease is caused and prolonged for so many people.”
Understanding the mechanism of the disease could point the way to ways of treating it, she says, and might also shed light on other cases of chronic disease associated with an initial viral infection. In particular, after recently finding that hospitalized COVID-19 patients harbor distinct antibodies against their own proteins, known as autoantibodies, she and her colleagues have begun investigating whether such autoantibodies are at play in long COVID.
Story by Shawna Williams, for The Scientist
24th Nov 2020
The ACGT hosted a webinar on “Nano-Engineering Gone Viral: Plant Virus-Based Therapies” presented by Prof Nicole Steinmetz from the University of California, San Diego. The webinar, held on the 3rd of November 2020, was part of the ACGT series of webinars introduced due to Covid-19 restricting physical meetings.
Prof Steinmetz’s interest in plant virus-based nanotechnology has been a lifelong academic interest of hers. She has been researching the field since her postgraduate years. The presentation took the audience on a journey of on how engineering plant viruses can be utilized for plant and human health. Prof Steinmetz highlighted that plant viruses (as a biologic material) offer high precision compared to synthetic systems which makes them an ideal therapeutic agent. The presentation then explored different applications of the technology which included molecular imaging to aid risk stratification, delivery of therapies, targeting plant health (pesticide delivery), and immunotherapy and vaccines.
Prof Steinmetz stated that “plant virus-based technologies could be produced ‘in the region for the region’ in developing countries lacking a conventional refrigeration system and health infrastructure, toward low-cost and edible therapeutics.” The “region for the region” concept could be realised with institutions such as the CSIR, who are active in this field, and others in the country engaging in collaborative efforts with local and international researchers such as Prof Steinmetz to produce region specific plant-based technologies.
The Centre has extended a research visit to Prof Steinmetz and are hopeful that she can visit the partnership as soon as travel restrictions allow.
To view the full webinar, please click here.
Story by: the ACGT
5th Nov 2020
The ACGT hosted a webinar-based workshop on “Biological Research via Top-down Proteomics” on the 9th of October. The workshop was facilitated by bioanalyst Professor David Tabb from Stellenbosch University’s Division of Molecular Biology and Human Genetics.
The workshop was another instalment of ACGT’s annual proteomics training workshops aimed at increasing capabilities in the field for South African researchers. Due to the pandemic, most of the Centre’s 2020 capacity building events had to be moved online, similar to international trends.
Professor Tabb, who has been with Stellenbosch University since 2015, has contributed immensely towards increasing informatics analyses capabilities within the South African proteomics community. He has previously partnered with the ACGT on a number of training workshops, in conjunction with international and local proteomics experts.
This advanced proteomics workshop described analytical chemistry advances that have made top-down proteomics research an area worth pursuing. The workshop also highlighted some research areas where top-down proteomics has been employed and proven to add valuable insights into complementary analyses, especially in the area of proteoforms.
The workshop was attended by 49 proteomics researchers from across South Africa as well as scientists from other African countries.
The workshop was aimed at stakeholders at various levels of laboratory and informatics analyses experience. It was also followed by a constructive question and answer session, where the need for collaboration in the country, as well as the need for utilizing a combination of proteomics technologies to address any particular biological question, were highlighted.
Click here to access the workshop recording.
Story by: The African Centre for Gene Technologies
2nd Nov 2020
Wits Professor of organic chemistry, Charles de Koning, recently won the South African Chemistry Institute’s (SACI) gold medal – the organisation’s top award. He was also inducted as a Fellow of SACI.
For De Koning, however, the award came as a bit of a surprise – since he wasn’t online during the announcement. As with most events this year, the SACI AGM and prizegiving took place virtually. “I had been on calls all day and decided to go cycling after work. When at some point I checked my phone, I saw that I had multiple missed calls,” says De Koning about the moment that he had found out that he had won the institute’s top prize.
The SACI only awards a single gold medal per year, to “a member of the Institute in good standing, whose scientific contributions in the field of chemistry or chemical technology are adjudged to be of outstanding merit”. De Koning has been involved with SACI since 1992 when he returned to South Africa after completing two post-doctoral stints abroad. He has served as treasurer for the SACI Gauteng branch and organised several conferences. The gold medal itself though is only one part of the award. De Koning will also deliver the gold medal plenary lecture at the next SACI symposium, and receive a cash prize.
De Koning’s research focuses on organic synthesis – organic chemistry using simple building blocks. By combining these building blocks, and developing new synthetic methods, new compounds can be assembled that have unique properties. In particular, De Koning who has built up a research profile of 136 peer-evaluated publications, and six book chapters throughout his career, is interested in the application of these new resources to human health and medicine.
In a high profile publication last year, De Koning and his team announced the discovery that cashew nut shells can be processed to extract building blocks for the manufacture of UV absorbent materials. Rather than focusing on dwindling petrochemical resources, De Koning’s team was able to source these building blocks from inedible waste products.
“By utilising these methods, this research has the potential to reveal many valuable compounds from renewable sources in the world around us,” says De Koning.
Beyond his research, De Koning considers his mentorship and supervision of students to be his greatest achievement – and the best part of the job. He has supervised a total of 36 PhD and 27 MSc students, many of whom have gone on to excel at careers in their own rights.
Some of his previous students, Willem van Otterlo, Edwin Mmutlane and Darren Riley, are now academics in organic chemistry at the University of Cape Town, the University of Johannesburg, and the University of Pretoria respectively. De Koning has also fostered a collaborative spirit with colleagues at two German universities, the Johannes Gutenberg-Universität Mainz and the University of Cologne, with which he has managed a student exchange programme over the past few decades.
De Koning’s interest in organic chemistry may have roots in his childhood – as a child he enjoyed playing with Lego.
“Back in the day there were no kits to build cars or spaceships, you just got the box of Lego pieces and made what was in your imagination,” he says. This interest in building blocks as a child, combined with a passion for organic synthesis during his undergraduate degree led to his successful career in “molecular engineering” through organic chemistry. Intrigued by the concept, De Koning went on to pursue a Masters and PhD on the subject, subsequently travelling from Boston to Hawaii before landing back in South Africa.
The SACI symposium at which De Koning will deliver his gold medal plenary lecture is set to take place in the Western Cape Province in 2021, although the dates may change given the current global Covid-19 pandemic.
Story and image by: The University of the Witwatersrand
26th Oct 2020
The African Centre for Gene Technologies (ACGT) and Metabolomics South Africa (MSA) hosted another successful metabolomics webinar on the 14th of October 2020. This Metabolomics webinar series serves as a platform for discussions on key technologies, techniques or new data analyses that could be of relevance to the rest of the South African metabolomics community.
Professor Justin J.J. van der Hooft, an Assistant Professor at Wageningen University, facilitated a webinar on the challenges of metabolite annotation and identification in untargeted metabolomics experiments of complex mixtures, typically encountered in natural products and food research. Untargeted metabolomics approaches are now widely used, spanning various disciplines including natural products discovery and “foodomics”. This webinar focused on how recently developed tools inspired by natural language processing, facilitate metabolomics analyses.
Prof van der Hooft is currently developing computational metabolomics methodologies to decompose complex metabolite mixtures aided by natural language processing and genomic tools. His interests are in plant- and microbiome-associated metabolites and the food metabolome as prime examples; where expanded knowledge on the specialized metabolome will assist in understanding key metabolic drivers of growth and health.
Similar to previous events, this webinar proved very popular to a diverse audience. It was attended by 102 participants from across South Africa, as well as from some international research institutions. There was a great Q&A session that followed and this highlighted the need for more of these sorts of meetings. The resources for those who wish to enter the field or perform a specific metabolomics application was also highlighted.The ACGT and MSA wishes to thank Prof van der Hooft for his superb webinar and look forward to collaborative opportunities in the field.
For a recording of this webinar, or for more information and suggestions about potential advanced biotechnology-related events, please contact Mr Molati Nonyane at .
12th Oct 2020
Africa’s leading research, development and innovation organisation, the Council for Scientific and Industrial Research (CSIR), has reached a major milestone, as today, 5 October 2020, marks 75 years of its existence.
Established in 1945, the CSIR has, for seven and a half decades, dedicated its resources to improving the quality of life of South Africans through ground-breaking research, development and innovation.
The organisation’s mandate has remained the intrinsic guiding force over the years, with the focus having been refined to respond to the global and local context. A refined focus resulted in, for example, the spin out of a number of institutions and the establishment of science councils, such as the South African Bureau of Standards, National Research Foundation, National Metrology Institute of South Africa, and the Human Sciences Research Council.
Professor Thokozani Majozi, Chairperson of the CSIR Board, said the organisation has a rich heritage and strong reputation for excellence and innovation.
“The CSIR is an exceptional organisation and our unique multidisciplinary capability, and the focus on making an impact in improving the quality of lives of South Africans is our steadfast pursuit. This outstanding feat bears testimony to the relevance of the CSIR and the role that it has played in our ecosystem of innovation since 1945. It has played an important role in shaping the country’s science, engineering and technology space,” said Prof Majozi.
Testament to that is the sound track record and reputation that the organisation has built based on leading research and technological development. Some of the most impactful CSIR innovations and inventions throughout the decades include the first radar in South Africa (1945), the first microwave electronic distance measurement equipment, the tellurometer (1954), as well as the contribution of CSIR research to the invention of the lithium-ion battery in the 1980s. Today, lithium-ion batteries power our smart phones, laptop computers, electric vehicles, smart grids and even our homes.
True to its multidisciplinary nature, the CSIR’s impact has been experienced in diverse fields. In 1999, CSIR researchers developed a forecasting model to predict the outcome of the national elections, based on early voting results. The model has since been successfully used to predict the results for all the national and local government elections. In 2010, the organisation unveiled its state-of-the-art containment Level 3 laboratory for experiments involving HIV and TB pathogens. It enables researchers to conduct research and proof-of-concept studies for new HIV/Aids and TB diagnostics or therapeutics.
The CSIR 75-year anniversary comes as the world faces the biggest pandemic in a century, Covid-19. Prof Majozi said the fact that the CSIR managed to step up to the plate to support the country in its efforts to curb the spread of the virus, demonstrates its uniqueness and relevance.
“We collaborated with a number of local partners to produce local ventilators that have been rolled out nationwide to patients showing respiratory distress in the early phase of Covid-19 infection. To date, 7 000 ventilators have been completed and delivered to hospitals and clinics.”
Over 18 000 Covid-19 tests have been conducted at an upgraded CSIR Biosafety Level 3 laboratory in a bid to boost the country’s testing capacity, in partnership with the National Health Laboratory Service. Work is underway to manufacture South Africa’s own Covid-19 sample purification kits in large quantities, creating a steady local supply that will speed up testing and reduce the country’s reliance on international suppliers amid intense global demand. The work is being funded by the Department of Science and Innovation, the South African Medical Research Council and the Technology Innovation Agency.
CSIR CEO, Dr Thulani Dlamini says that the anniversary is not only for celebrating, but also engaging deeper with the CSIR’s vision, mission, values and future as a leading scientific and technology research organisation.
“More than ever, our country needs technological innovation for socioeconomic development, which is the only way to improve the lives of the people of South Africa. We have sharpened our focus to achieve this – we have developed a new strategy to specifically address industrial development, along with our aim of supporting a capable state.”
“Our new strategy will create a science council that plays a more visible role in industrial development, underpinned by a strong scientific and innovation capability. The strategy focuses on getting our scientists, engineers and technicians to work more closely with private sector companies in their innovation efforts, and it is upheld by the four pillars of growth, sustainability, impact and relevance”, says Dlamini.
Dlamini adds, “As part of the celebrations, we will host our 7th Biennial CSIR Conference on 11 and 12 November. Not only will we be sharing some of our exciting and impactful work, but we will also debate and discuss some of the challenges that technological innovation can help address with industry and government stakeholders. The virtual event will comprise a series of online events, including webinars, virtual tours, demonstrations and exhibitions.”
Story by:CSIR Strategic Communication unit
8th Oct 2020
The gene-editing technique CRISPR earned the 2020 Nobel Prize in chemistry. Recognition of this amazing breakthrough technology is well deserved.
But each Nobel Prize can be awarded to no more than three people, and that’s where this year’s prize gets really interesting.
Editing letters in the book of life
CRISPR is a powerful gene-editing tool that has taken molecular biology from the typewriter to the word processor age. One could say it’s like Microsoft Word for the book of life. CRISPR allows a researcher to find not just a gene, but a very specific part of a gene and change it, delete it or add a completely foreign gene. Genetic modifications that used to take sophisticated biological laboratories years to do are now done in days and at significantly less cost.
The CRISPR story begins in 1987, when molecular biologist Yoshizumi Ishino and his co-workers discovered a strange palindromic stretch of DNA in E. coli, a commonly studied stomach bacteria. No one could imagine what purpose it served.
Nearly two decades later, at the National Center for Biotechnology Information in Bethesda, Maryland, Eugene Koonin established the odd DNA’s function as a bacterial defense system composed of two parts. The first is a stretch of DNA that acts as an album of vanquished foes. When the bacterium overcomes an enemy, it snips out a section of the defeated invaders’ genetic material and places it into the album. These genetic mug shots are separated by repetitive stretches of DNA that read the same forward or backward. These bits of DNA are called Clustered Regularly Interspaced Short Palindromic Repeats – CRISPR for short.
The second component of the bacterial defense system is a search-and-destroy weapon. Each genetic mug shot has a search-and-destroy protein associated with it called a CRISPR-associated (Cas) protein. These Cas proteins circulate inside the cell, and when they encounter a stretch of genetic material corresponding to their genetic mug shot target, they kill the invader.
It took 20 years and much research to discover and understand these proteins.
Then in 2007, Danisco, a Danish food and beverage company, confirmed Koonin’s hypothesis that CRISPR is a bacterial defense system. Today, most yogurt and cheese manufacturers include CRISPR sequences in their cultures to protect their products from common viral outbreaks. According to Rodolphe Barrangou, who conducted this research at Danisco USA: “If you’ve eaten yogurt or cheese, chances are you’ve eaten CRISPR-ized cells.”
Harnessing CRISPR’s potential
Jennifer Doudna, a biochemist with extensive experience working with RNA at the University of California, Berkeley, started working with CRISPR in 2006. At a 2011 American Society for Microbiology meeting in San Juan, Puerto Rico, she met Emmanuelle Charpentier, an associate professor at the Laboratory for Molecular Infection Medicine Sweden at Umeå, who worked on a particular CRISPR-associated protein called Cas9.
Doudna and Charpentier had complementary skills. While walking around the old town of San Juan, Charpentier convinced Doudna that Cas9 was responsible for finding the DNA sequence that corresponds to the mug shot and cutting it. Doudna was intrigued and agreed to take a closer look at the role Cas9 played.
Charpentier worked with Cas9 in Streptococcus pyogenes, the bacteria that cause strep throat and flesh-eating disease. Rather than send Doudna these dangerous bacteria, she overnighted her the DNA encoding the CRISPR-Cas9. The more Doudna studied Charpentier’s molecular scissors, the more obvious it became to her that this bacterial system could be co-opted to edit DNA. She was right, and with some tweaking, she converted CRISPR-Cas9 into a gene editing tool. Doudna noted in her memoir that CRISPR-Cas9 “was the perfect bacterial weapon: a virus-seeking missile that could strike quickly and with incredible precision.”
Doudna and her collaborators wrote up their results and submitted their manuscript to the journal Science, which fast-tracked the paper and published it days after submission. Around the same time, she filed a patent application for the CRISPR-Cas9 gene-editing system.
Meanwhile, Virginijus Siksnys, a molecular biologist at Vilnius University in Lithuania with a research background in a class of proteins that cut DNA called restriction endonucleases, also foresaw the CRISPR system’s potential. He submitted his own results to the journal Cell. The editor rejected the manuscript without sending it out for review. Siksnys, confident in his work and its importance, submitted his manuscript to the Proceedings of the National Academy of Sciences. The paper was sent in before Doudna’s paper was published, but it needed some revisions and was thus published three months after Doudna’s paper appeared.
Like Doudna and Siksnys, Feng Zhang, a professor of neuroscience at MIT, was using the CRISPR-Cas9 system to edit DNA. But while the others did all their editing in solution, Zhang was slicing and dicing DNA with CRISPR-Cas9 in human cells. In January 2013, Zhang published his own Science paper. At this time, even though Doudna had applied for a patent seven months earlier, Feng Zhang asked his employers, MIT and the Broad Institute, to file a patent on his behalf.
The Broad Institute lawyers, knowing that Doudna’s claim was pending, paid an additional fee to accelerate their patent application. It worked, and they were granted a CRISPR-Cas9 patent before Doudna was eventually awarded hers. This has started a closely watched legal battle. The contest is far from over, but it seems that Doudna is winning the legal battle in the EU and Zhang in the U.S.
Politics around the prize
The decision to award the Nobel Prize to Doudna and Charpentier couldn’t have been easy. By choosing these two over Feng Zhang, the Royal Swedish Academy of Sciences sent a major message. It could have awarded the prize to a third researcher, but it didn’t. Was it a statement intended for the legal system?
Fortunately, scientists using CRISPR as a molecular editor aren’t affected by the legal battles. They can get their CRISPR systems from the Addgene open-source repository. Clinical applications of CRISPR – like finding a cure for genetic diseases such as cystic fibrosis and sickle cell anemia – will most likely be affected by the legal wranglings, as that is the technology’s most commercial use.
Often, basic science research goes nowhere. Often it goes in unexpected directions. Sometimes it leads to the most excitingly splendid conclusions. CRISPR-Cas9 is one of these cases. It started with a weirdly repeating palindrome, matured via mozzarella and yogurt and finally blossomed into a contested gene-editing tool that was awarded the 2020 Nobel Prize.
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28th Sep 2020
The ACGT and MSA would like to congratulate Dr Fidele Tugizimana, the current chairman of Metabolomics South Africa (MSA), on his appointment to the board of directors for the International Metabolomics Society (IMS). Dr Tugizimana is a research scientist with the plant metabolomics research group at the University of Johannesburg. He is also a specialist scientist in the international R&D management of the Omnia (Pty) Ltd company (SA) and a scientific consultant in the L.E.A.F. Pharmaceuticals LLC (USA & Rwanda). Dr Tugizimana’s metabolomics research interests include host-pathogen interactions, immune response (at molecular level), chemometrics, bioinformatics and metabolite identification. He is an author/co-author of metabolomics papers in leading peer-reviewed scientific journals.
This appointment to the board of directors follows previous leadership involvement with the International Metabolomics Society as a secretary of the Early-career members Network (EMN) committee (2016-2017); (ii) member of the Data Standards and Strategy Tasks groups; and (iii) member of the International Organizing Committee for the International Metabolomics Conferences 2017 and 2019. The ACGT and MSA would like to congratulate its longtime partner and friend, Dr Tugizimana on his new role and we wish him all the luck.
11th Aug 2020
South Africa is on track to manufacture its own Coronavirus disease 2019 (COVID-19) sample purification kits in large quantities within six months, creating a steady local supply that will speed up testing and reduce the country’s reliance on international suppliers amid intense global demand.
The CSIR’s Dr Previn Naicker says the technology being developed by his team is open source in that it would generate pure samples from nasal and throat swabs that can be tested for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA on any platform. The work is being funded by the Department of Science and Innovation, the South African Medical Research Council and the Technology Innovation Agency.
A reliable local supply of sample purification reagents also addresses the specific problem of patient swabs becoming non-viable for testing because of the lengthy backlogs caused by a lack of reagents. Not only do such long waiting periods compromise test results for individual patients, it compromises the entire disease management process that relies on quarantine along with quick contact tracing and testing.
“There are testing facilities that are not running at full capacity because there are not enough diagnostic reagents,” Naicker says. “The project will ensure that we close that gap and reduce the turnaround time of testing.”
The CSIR is working with local partners such as ReSyn Biosciences, a spin-off company of the CSIR that will produce magnetic beads for extracting viral RNA from test samples.
Magnetic beads offer the advantage that RNA extraction can be automated. “Every step of the diagnostic process that can be automated makes for better testing,” says Naicker.
As positive cases in South Africa continue to increase at an alarming rate, Naicker says the portion of positive cases in relation to the tests conducted shows that South Africa is under-testing. Experts say the virus will be with us for a long time to come, so Naicker’s team and their local partners plan to optimise the kit within the next two months so that validation (testing on real samples), licencing and regulatory approval by the South African Health Products Regulation Authority (SAHPRA) can take place as soon as possible.
“If all goes according to plan, we will have a market-ready kit within six months,” says Naicker.
“Based on the capacity of our local partners, kits for the extraction of a minimum of 5 000 samples can be assembled per day at a certified facility, and we are in discussions with two proposed facilities thus far.” In other words, this technology could support at least an additional 10 000 COVID-19 tests per day.
“As a scientist working in the health space, to be part of the COVID-19 response is both fulfilling and exciting,” he says. “We all have a desire to make a positive societal impact.”
Story by: Council of Scientific and Industrial Research