In May 2022, a clinical trial quietly got under way in London when a British teenager named Alyssa became the first patient to receive an experimental treatment generated using “base-editing”, an emerging form of DNA engineering. Alyssa, 13, had exhausted all conventional treatments for a difficult-to-treat blood cancer, and was enrolled to receive immune cells from a healthy volunteer that had been programmed to hunt and kill leukaemia cells. Within a month, the disease was undetectable.
Whether this highly sophisticated form of cell therapy, undertaken by our team at London’s Great Ormond Street Hospital, has cleared the cancer permanently, and whether subsequent patients will also respond, only time will tell. Nonetheless, the breathless pace of research developments around gene therapies, with ever impressive technological improvements, are with good reason, providing scope for optimism.
It is almost 20 years since the Human Genome Project, an international research programme involving 20 universities across six countries, completed a decade-long quest to sequence the DNA code, which makes up our genes and chromosomes. Some 3 billion pairs of letters – or bases – were found to be organised into 20,000 or more genes, and which ultimately guard and control the secrets of life in every nucleated cell.
The code encrypted into bundles, or genes, relies on just four DNA bases and carries instructions to molecular machinery found inside cells and orders the production of proteins. If DNA code is the script, proteins are actors playing out their roles to determine how cells assemble, develop, function, interact, sleep, wake, replicate and die.
At the turn of the millennium, there was still a great deal of uncertainty around how quickly these enormous data sets might be exploited to improve human health. Variations in the DNA code arise naturally between individuals, and occasionally some changes – commonly known as mutations – give rise to diseases. Some dominant mutations – for example, for the neurodegenerative disorder Huntington’s disease – act alone. Other mutations – as in the case of the inherited blood disorder beta thalassemia or lung disease cystic fibrosis – are problematic only in combination.
The question being asked then was, how can mutations be permanently corrected or their effects reversed? A handful of early reports of successful “genetic therapies” were emerging at the time.
The holy grail of gene therapy remains a quest to replace or change DNA 'on site' in a single, efficient and reliable therapy
For example, in France in 2001, the paediatric immunologists Alain Fischer and Maria Cavazzano used a modified virus, gutted of its own genes, to carry a therapeutic gene into bone marrow cells collected from infants born without a functioning immune system. Return of these “repaired” stem cells back to the infants supported life-saving recovery, restoring immunity and clearing infections.
Later, it became apparent that pushing extra copies of genes randomly into chromosomes can disrupt how cells proliferate and might, in some circumstances, cause cancer. This prompted researchers to revise and upgrade the virus delivery systems. As a result, today there are dozens of experimental treatments being investigated to add extra copies of genes to cells. Some therapies have reached the stage of market authorisation, including for beta thalassemia and certain forms of haemophilia, which otherwise require life-long blood product support. Overall, numbers treated to date are relatively small, and long-term monitoring will give us a better picture of their effectiveness and safety. For now, exceptional price tags will raise eyebrows and restrict access, but developments continue at a rapid pace, and improved, safer and more effective strategies are all but inevitable.
The holy grail of gene therapy remains a quest to replace or change DNA “on site” in a single, efficient and reliable therapy. That aspiration was boosted in 2012, when an enzyme system called Crispr/Cas9, first discovered in bacteria, was repurposed to precisely cut or snip human DNA. This was not the first such platform to be developed. In fact, our team had deployed existing molecular scissor tools for editing “T cells” – a type of white blood cells that are a part of the immune system – against leukaemia. However, Crispr is a highly adaptable, inexpensive and easy-to-use technology. It is indeed a breakthrough technology that earned its developers, Emmanuelle Charpentier and Jennifer Doudna, the 2020 Nobel Prize in Chemistry.
Simultaneous advances in sequencing technologies and computing power now enable an entire genome to be sequenced within hours. A new wave of therapeutic strategies are already in development. A number of clinical trials using Crispr/Cas9 are under way, mostly to disrupt genes, including at our hospital where earlier this year, we published how Crispr can more efficiently engineer T cells.
This week, at the American Society of Haematology annual conference in New Orleans, we reported how an even newer generation of molecular tools – called base-editors – are being applied to generate “off-the-shelf” T cells to treat other types of aggressive leukaemia.
Base-editors were invented at the Massachusetts Institute of Technology, as recently as 2016, and can chemically change single letters of the DNA code. The technology draws on the guidance system of Crispr to reach very precise locations on chromosomes, deep inside the centre of cells. Rather than cut DNA, the molecular machines deploy localised chemistry to change letters just within reach of their enzyme arms. The cells that Alyssa received were the most complex generated so far, and she went into remission within a month of treatment.
All this is very encouraging, but of course more patients will need to be treated and followed over a much longer period of time, in this and other clinical trials.
Nonetheless, a quite remarkable technological leap is under way, and it seems highly likely that there will be further iterations and clever refinements to come. Solutions to address delivery into other types of cells, and to limit possible immune responses, are being investigated. New questions and dilemmas will be certain to arise, not least around regulatory oversight, costs and accessibility of these cutting-edge technologies as the revolution unfolds.
For now at least, one relieved family will celebrate the holidays together, and there is hope for others into a new year.
Key figures in the life of the fort
Sheikh Dhiyab bin Isa (ruled 1761-1793) Built Qasr Al Hosn as a watchtower to guard over the only freshwater well on Abu Dhabi island.
Sheikh Shakhbut bin Dhiyab (ruled 1793-1816) Expanded the tower into a small fort and transferred his ruling place of residence from Liwa Oasis to the fort on the island.
Sheikh Tahnoon bin Shakhbut (ruled 1818-1833) Expanded Qasr Al Hosn further as Abu Dhabi grew from a small village of palm huts to a town of more than 5,000 inhabitants.
Sheikh Khalifa bin Shakhbut (ruled 1833-1845) Repaired and fortified the fort.
Sheikh Saeed bin Tahnoon (ruled 1845-1855) Turned Qasr Al Hosn into a strong two-storied structure.
Sheikh Zayed bin Khalifa (ruled 1855-1909) Expanded Qasr Al Hosn further to reflect the emirate's increasing prominence.
Sheikh Shakhbut bin Sultan (ruled 1928-1966) Renovated and enlarged Qasr Al Hosn, adding a decorative arch and two new villas.
Sheikh Zayed bin Sultan (ruled 1966-2004) Moved the royal residence to Al Manhal palace and kept his diwan at Qasr Al Hosn.
Sources: Jayanti Maitra, www.adach.ae
The specs
Engine: 3.0-litre six-cylinder turbo
Power: 398hp from 5,250rpm
Torque: 580Nm at 1,900-4,800rpm
Transmission: Eight-speed auto
Fuel economy, combined: 6.5L/100km
On sale: December
Price: From Dh330,000 (estimate)
The National's picks
4.35pm: Tilal Al Khalediah
5.10pm: Continous
5.45pm: Raging Torrent
6.20pm: West Acre
7pm: Flood Zone
7.40pm: Straight No Chaser
8.15pm: Romantic Warrior
8.50pm: Calandogan
9.30pm: Forever Young
The Kingfisher Secret
Anonymous, Penguin Books
Match info:
Portugal 1
Ronaldo (4')
Morocco 0
Moving%20Out%202
%3Cp%3E%3Cstrong%3EDeveloper%3A%3C%2Fstrong%3E%20SMG%20Studio%3Cbr%3E%3Cstrong%3EPublisher%3A%3C%2Fstrong%3E%20Team17%3Cbr%3E%3Cstrong%3EConsoles%3A%3C%2Fstrong%3E%20Nintendo%20Switch%2C%20PlayStation%204%26amp%3B5%2C%20PC%20and%20Xbox%20One%3Cbr%3E%3Cstrong%3ERating%3A%3C%2Fstrong%3E%204%2F5%3C%2Fp%3E%0A
Veere di Wedding
Dir: Shashanka Ghosh
Starring: Kareena Kapoo-Khan, Sonam Kapoor, Swara Bhaskar and Shikha Talsania
Verdict: 4 Stars
Your Guide to the Home
- Level 1 has a valet service if you choose not to park in the basement level. This level houses all the kitchenware, including covetable brand French Bull, along with a wide array of outdoor furnishings, lamps and lighting solutions, textiles like curtains, towels, cushions and bedding, and plenty of other home accessories.
- Level 2 features curated inspiration zones and solutions for bedrooms, living rooms and dining spaces. This is also where you’d go to customise your sofas and beds, and pick and choose from more than a dozen mattress options.
- Level 3 features The Home’s “man cave” set-up and a display of industrial and rustic furnishings. This level also has a mother’s room, a play area for children with staff to watch over the kids, furniture for nurseries and children’s rooms, and the store’s design studio.
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%3Cp%3E%3Cstrong%3EDeveloper%3A%20%3C%2Fstrong%3ERemedy%20Entertainment%3Cbr%3E%3Cstrong%3EPublisher%3A%3C%2Fstrong%3E%20Microsoft%20Game%20Studios%3Cbr%3E%3Cstrong%3EConsoles%3A%3C%2Fstrong%3E%20PlayStation%204%20%26amp%3B%205%2C%20Xbox%3A%20360%20%26amp%3B%20One%20%26amp%3B%20Series%20X%2FS%20and%20Nintendo%20Switch%3Cbr%3E%3Cstrong%3ERating%3A%3C%2Fstrong%3E%204%2F5%3C%2Fp%3E%0A
BMW M5 specs
Engine: 4.4-litre twin-turbo V-8 petrol enging with additional electric motor
Power: 727hp
Torque: 1,000Nm
Transmission: 8-speed auto
Fuel consumption: 10.6L/100km
On sale: Now
Price: From Dh650,000
Specs
Engine: Electric motor generating 54.2kWh (Cooper SE and Aceman SE), 64.6kW (Countryman All4 SE)
Power: 218hp (Cooper and Aceman), 313hp (Countryman)
Torque: 330Nm (Cooper and Aceman), 494Nm (Countryman)
On sale: Now
Price: From Dh158,000 (Cooper), Dh168,000 (Aceman), Dh190,000 (Countryman)
Electoral College Victory
Trump has so far secured 295 Electoral College votes, according to the Associated Press, exceeding the 270 needed to win. Only Nevada and Arizona remain to be called, and both swing states are leaning Republican. Trump swept all five remaining swing states, North Carolina, Georgia, Pennsylvania, Michigan and Wisconsin, sealing his path to victory and giving him a strong mandate.
Popular Vote Tally
The count is ongoing, but Trump currently leads with nearly 51 per cent of the popular vote to Harris’s 47.6 per cent. Trump has over 72.2 million votes, while Harris trails with approximately 67.4 million.
Mohammed bin Zayed Majlis
Company Profile
Founder: Omar Onsi
Launched: 2018
Employees: 35
Financing stage: Seed round ($12 million)
Investors: B&Y, Phoenician Funds, M1 Group, Shorooq Partners
if you go
The flights
Fly to Rome with Etihad (www.etihad.ae) or Emirates (www.emirates.com) from Dh2,480 return including taxes. The flight takes six hours. Fly from Rome to Trapani with Ryanair (www.ryanair.com) from Dh420 return including taxes. The flight takes one hour 10 minutes.
The hotels
The author recommends the following hotels for this itinerary. In Trapani, Ai Lumi (www.ailumi.it); in Marsala, Viacolvento (www.viacolventomarsala.it); and in Marsala Del Vallo, the Meliaresort Dimore Storiche (www.meliaresort.it).
Killing of Qassem Suleimani
UAE currency: the story behind the money in your pockets
Global Fungi Facts
• Scientists estimate there could be as many as 3 million fungal species globally
• Only about 160,000 have been officially described leaving around 90% undiscovered
• Fungi account for roughly 90% of Earth's unknown biodiversity
• Forest fungi help tackle climate change, absorbing up to 36% of global fossil fuel emissions annually and storing around 5 billion tonnes of carbon in the planet's topsoil
Moral education needed in a 'rapidly changing world'
Moral education lessons for young people is needed in a rapidly changing world, the head of the programme said.
Alanood Al Kaabi, head of programmes at the Education Affairs Office of the Crown Price Court - Abu Dhabi, said: "The Crown Price Court is fully behind this initiative and have already seen the curriculum succeed in empowering young people and providing them with the necessary tools to succeed in building the future of the nation at all levels.
"Moral education touches on every aspect and subject that children engage in.
"It is not just limited to science or maths but it is involved in all subjects and it is helping children to adapt to integral moral practises.
"The moral education programme has been designed to develop children holistically in a world being rapidly transformed by technology and globalisation."
UAE currency: the story behind the money in your pockets
The%20specs
%3Cp%3E%3Cstrong%3EEngine%3A%3C%2Fstrong%3E%20Twin%20electric%20motors%20and%20105kWh%20battery%20pack%0D%3Cbr%3E%3Cstrong%3EPower%3A%20%3C%2Fstrong%3E619hp%0D%3Cbr%3E%3Cstrong%3ETorque%3A%20%3C%2Fstrong%3E1%2C015Nm%0D%3Cbr%3E%3Cstrong%3ETransmission%3A%20%3C%2Fstrong%3ESingle-speed%20auto%0D%3Cbr%3E%3Cstrong%3ETouring%20range%3A%20%3C%2Fstrong%3EUp%20to%20561km%0D%3Cbr%3E%3Cstrong%3EOn%20sale%3A%20%3C%2Fstrong%3EQ3%20or%20Q4%202022%0D%3Cbr%3E%3Cstrong%3EPrice%3A%20%3C%2Fstrong%3EFrom%20Dh635%2C000%3C%2Fp%3E%0A
Why are asylum seekers being housed in hotels?
The number of asylum applications in the UK has reached a new record high, driven by those illegally entering the country in small boats crossing the English Channel.
A total of 111,084 people applied for asylum in the UK in the year to June 2025, the highest number for any 12-month period since current records began in 2001.
Asylum seekers and their families can be housed in temporary accommodation while their claim is assessed.
The Home Office provides the accommodation, meaning asylum seekers cannot choose where they live.
When there is not enough housing, the Home Office can move people to hotels or large sites like former military bases.
Ferrari 12Cilindri specs
Engine: naturally aspirated 6.5-liter V12
Power: 819hp
Torque: 678Nm at 7,250rpm
Price: From Dh1,700,000
Available: Now
More from Neighbourhood Watch:
Diriyah%20project%20at%20a%20glance
%3Cp%3E-%20Diriyah%E2%80%99s%201.9km%20King%20Salman%20Boulevard%2C%20a%20Parisian%20Champs-Elysees-inspired%20avenue%2C%20is%20scheduled%20for%20completion%20in%202028%0D%3Cbr%3E-%20The%20Royal%20Diriyah%20Opera%20House%20is%20expected%20to%20be%20completed%20in%20four%20years%0D%3Cbr%3E-%20Diriyah%E2%80%99s%20first%20of%2042%20hotels%2C%20the%20Bab%20Samhan%20hotel%2C%20will%20open%20in%20the%20first%20quarter%20of%202024%0D%3Cbr%3E-%20On%20completion%20in%202030%2C%20the%20Diriyah%20project%20is%20forecast%20to%20accommodate%20more%20than%20100%2C000%20people%0D%3Cbr%3E-%20The%20%2463.2%20billion%20Diriyah%20project%20will%20contribute%20%247.2%20billion%20to%20the%20kingdom%E2%80%99s%20GDP%0D%3Cbr%3E-%20It%20will%20create%20more%20than%20178%2C000%20jobs%20and%20aims%20to%20attract%20more%20than%2050%20million%20visits%20a%20year%0D%3Cbr%3E-%20About%202%2C000%20people%20work%20for%20the%20Diriyah%20Company%2C%20with%20more%20than%2086%20per%20cent%20being%20Saudi%20citizens%0D%3C%2Fp%3E%0A
War 2
Director: Ayan Mukerji
Stars: Hrithik Roshan, NTR, Kiara Advani, Ashutosh Rana
Rating: 2/5
Results
- Brock Lesnar retained the WWE Universal title against Roman Reigns
- Braun Strowman and Nicolas won the Raw Tag Team titles against Sheamus and Cesaro
- AJ Styles retained the WWE World Heavyweight title against Shinsuke Nakamura
- Nia Jax won the Raw Women’s title against Alexa Bliss
- Daniel Bryan and Shane McMahon beat Kevin Owens and Sami Zayn
- The Undertaker beat John Cena
- The Bludgeon Brothers won the SmackDown Tag Team titles against the Usos and New Day
- Ronda Rousey and Kurt Angle beat Triple H and Stephanie McMahon
- Jinder Mahal won the United States title against Randy Orton, Rusev and Bobby Roode
- Charlotte retained the SmackDown Women’s title against Asuka
- Seth Rollins won the Intercontinental title against The Miz and Finn Balor
- Naomi won the first WrestleMania Women’s Battle Royal
- Cedric Alexander won the vacant Cruiserweight title against Mustafa Ali
- Matt Hardy won the Andre the Giant Battle Royal
Conflict, drought, famine
Estimates of the number of deaths caused by the famine range from 400,000 to 1 million, according to a document prepared for the UK House of Lords in 2024.
It has been claimed that the policies of the Ethiopian government, which took control after deposing Emperor Haile Selassie in a military-led revolution in 1974, contributed to the scale of the famine.
Dr Miriam Bradley, senior lecturer in humanitarian studies at the University of Manchester, has argued that, by the early 1980s, “several government policies combined to cause, rather than prevent, a famine which lasted from 1983 to 1985. Mengistu’s government imposed Stalinist-model agricultural policies involving forced collectivisation and villagisation [relocation of communities into planned villages].
The West became aware of the catastrophe through a series of BBC News reports by journalist Michael Buerk in October 1984 describing a “biblical famine” and containing graphic images of thousands of people, including children, facing starvation.
Band Aid
Bob Geldof, singer with the Irish rock group The Boomtown Rats, formed Band Aid in response to the horrific images shown in the news broadcasts.
With Midge Ure of the band Ultravox, he wrote the hit charity single Do They Know it’s Christmas in December 1984, featuring a string of high-profile musicians.
Following the single’s success, the idea to stage a rock concert evolved.
Live Aid was a series of simultaneous concerts that took place at Wembley Stadium in London, John F Kennedy Stadium in Philadelphia, the US, and at various other venues across the world.
The combined event was broadcast to an estimated worldwide audience of 1.5 billion.
Key facilities
- Olympic-size swimming pool with a split bulkhead for multi-use configurations, including water polo and 50m/25m training lanes
- Premier League-standard football pitch
- 400m Olympic running track
- NBA-spec basketball court with auditorium
- 600-seat auditorium
- Spaces for historical and cultural exploration
- An elevated football field that doubles as a helipad
- Specialist robotics and science laboratories
- AR and VR-enabled learning centres
- Disruption Lab and Research Centre for developing entrepreneurial skills
Specs
Engine: Duel electric motors
Power: 659hp
Torque: 1075Nm
On sale: Available for pre-order now
Price: On request
