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PARIS — Two French restaurants tasted the ultimate accolade in top-level gastronomy on Monday, winning three coveted Michelin stars in the guide’s 2015 edition.

“La Bouitte” in the French Alps, run by father-and-son team Rene and Maxime Meilleur and Yannick Alleno’s Parisian restaurant “Ledoyen” joined the pantheon of top eateries in the self-styled home of gastronomy.

Rene, 64, and Maxime, 39, were awarded the industry’s top prize for their “extraordinary” skills with fish, said Michael Ellis, director of international guides for Michelin.

The food bible hailed the Alpine chalet restaurant, located at an altitude of 2,500 metres, as “generous, authentic and full of emotion”.

The fishy delights on the menu include trout, scallops and crawfish, while meat eaters can tuck into frogs’ legs with black garlic and watercress, duck foie gras escalope, sweetbreads and venison.

But such three-star cuisine does not come cheap. A three-course “surprise” menu will set you back 115 euros ($130), while an eight-course banquet weighs in at 225 euros.

‘Explosion of flavour’

Away from the snowy mountains, “Ledoyen”, near the capital’s famed Champs Elysees, retained its three-star status but with a new chef, the 46-year-old Alleno, at the pass.

Alleno, who already won three stars in 2007 for his work at Le Meurice in Paris, was cited for his skill with sauces.

He has perfected an “extraction” technique for sauces, resulting in an ultra-pure jus with an intense flavour.

“We found a Yannick Alleno at the top of his game,” said Ellis.

“The techniques have been mastered in an extraordinary fashion. The concentration and explosion of flavour are quite simply remarkable,” he added.

He singled out for special praise a souffle of smoked eel with a watercress reduction and a brioche of pike with celery extract.

While the champagne corks were popping there, others were left crying into their soup as they were demoted to “mere” two-star status.

The “Arnsbourg” in eastern France was relegated from three stars to two following the departure of chef Jean-Georges Klein.

And “La Cote Saint-Jacques”, in central France, had a star removed due to a “lack of consistency in certain dishes”.

The 2015 guide crowned 26 three-star restaurants in France, one fewer than last year. Worldwide, there are 111.

There were 80 two-star restaurants (seven of which were new) and 503 one-star restaurants (37 of them making the grade for the first time).

In total, there are now 609 Michelin-starred restaurants in France.

The criterion for winning three stars is that the restaurant must serve up “exceptional cuisine, worth a special journey”.

The three previous editions of the guide crowned one new three-starred chef each and none in 2011.

Last year, the most coveted accolade in gastronomy went to Arnaud Lallement, of the family-run L’Assiette Champenoise near Reims in northeastern France.

The new guide was unveiled at the French foreign ministry, which is determined to maintain the country’s reputation as the top destination for foodies.

Last week, an American food critic threw salt in Michelin’s sauce by declaring that most of the top Paris listings were not worth their exorbitant prices.

Meg Zimbeck, who runs Paris By Mouth, a respected online review site that also provides foodie tours to English-speaking visitors, backed up her argument with research: four months of anonymous dining in all Paris restaurants boasting two or three Michelin stars.

What she found, after booking into 16 restaurants under false names and paying a total 7,150 euros for the meals, was that Michelin’s recommendations didn’t always deliver.

Amman — Traditional Indian saris exhibited Sunday at Galleria Ras Al Ain captured visitors’ attention with their vibrancy, brightness and exquisite patterns.

Each sari on display tells a different story from the heritage of the vast civilisation of India. 

Dating back to 2800 BC, the sari continues to be an artistic statement that personifies India and Indian women.

“Throughout the years, the Indian sari and India have become synonymous,” Anupama Trigunayat, wife of the Indian ambassador to Jordan, told The Jordan Times.

“The sari still holds that special place because it is at the core of the life of Indian women,” she said, highlighting the workmanship of Indian weavers.

The exhibition, called “Sari: The Magic of Indian Weaves”, was inaugurated by HRH Princess Basma who commended the Jordanian-Indian cooperation, in whose spirit the exhibition of the saris is held.

Indian textiles and saris represent a great heritage, she said, highlighting the grace and appeal of saris.

Indian Ambassador to Jordan Anil Trigunayat said saris — the word is derived from Sanskrit “sati”, which means strip of cloth — used to be one piece of cloth in the old days, as wearing stitched clothes was believed to be impure.

“When we thought of cultural activities to bring a little bit of India to Jordan, we thought of saris,” said the ambassador. 

Curated by Rta Kapur Chishti, the exhibition drew quite an attendance on the first day.

Sue Mullin, president of the International Women’s Association, Amman, said it is interesting to see the traditional saris, which can be distinguished by states and areas, according to the pattern.

“Likewise, it is nice to see the contemporary designs which you cannot tell where they come from,” she said.

Today’s sari has three parts: the sari itself, a short blouse that is separately stitched and an underskirt, a petticoat, said the envoy’s wife, adding that a sari is usually a six to nine-metre strip of fabric.

The blouse covers the bust and can be short or long sleeved, she said, adding that traditionally, it was believed that the navel symbolises life, creation of life, “so you keep it visible”.

Visitor Parveen Rahman, a Bengali physician living in Jordan, said saris are easy to wear.

“There are some folds and you have to make the pleats,” said another visitor.

Colours are also symbolic, said Mrs. Trigunayat; red and orange, and their different nuances, are very auspicious, for example.

Bright colours are usually worn at weddings and the quality of the fabric depends on the season.

Silk is worn in winter and sometimes in spring. Silk saris from the south of India are famous for their bright colours and are embellished with gold motifs. Saris from the north are usually embellished with brocade.

“Today, there are 80 ways of draping a sari,” she added, depending on the area. 

The exhibition will run until February 10 as part of several cultural activities held in Amman this month, including a Bollywood film festival, marking 65 years of cooperation between Jordan and India.

The Plague of Doves

Louise Erdrich

London: Harper Perennial, 2008

Pp. 311

Spanning four generations, Louise Erdrich tells the story of Pluto, a fictitious town in North Dakota, and the adjacent Indian reservation. Or rather, she lets three of her characters tell their stories, then gives the final word to a fourth character who puts a whole new spin on the entire saga.

This is part of the point: There are many sides to every story; history is complicated. It does not mean that there is no right or wrong, but the dividing line between the two is not always as clear-cut as it may appear, especially if one takes into account the role of motives, chance and coercion. 

As the different narratives intersect, new insights and layers of understanding are added to the events and characters, and what a cast of characters Erdrich has invented! There are the pious, the pretenders and the truly spiritual, visionaries and adventurers, criminals, artists, dedicated professionals, philosophers, lovers of the land, unscrupulous landgrabbers, bigots, dreamers, and the slightly or totally crazy. Even more intriguing, many characters fall into more than one category. 

There is no rigid demarcation between the inhabitants of Pluto and the reservation as one might expect. Originally, it was white settlers who established Pluto on the land of the Chippewa or Ojibwe, one of the largest Native American groups whose territory spanned what is now the US-Canadian border. 

Yet, from the beginning, the lives of newcomers and natives began to intersect in so many ways. There was much intermarriage as well as off-the-record interbreeding, but most of all, the community was tangled together by a shared history that included the brutal murder of a white family, and the random lynching of a group of Chippewa who happened to be in the vicinity. 

Judge Antone Bazil Coutts, who narrates part of the story, is one of many who straddles the divide, being part white and part Chippewa, and thus well-placed to balance between tribal, federal and state law. He knows both sides of the cases he hears, and fills the reader in on the secrets and entanglements of the community’s shared history, concluding, “nothing that happens, nothing, is not connected here by blood.” (p. 115)

The tangled history of the community gives rise to many ironies, some of them tragic, as someone may end up killing a person whose grandfather saved one of their ancestors. While many of the adults harbour grudges because of past wrongs, they go about their lives knowing that some things cannot be changed. As Evelina, a young narrator, says after learning about the community’s history from her grandfather’s rambling reminiscences, “now that some of us have mixed in the spring of our existence both guilt and victim, there is no unravelling the rope.” (p. 243)

“The Plague of Doves” contains so many characters and subplots that one is amazed by how the author ties them together across families and time, in her graceful, lyrical and sensuous style. Her imagination seems to know no bounds. Not only people and lineage provide continuity but also objects, such as a violin fought over by two brothers and lost to both. Standing as a powerful symbol of the endurance of Ojibwe culture, it magically re-emerges decades later to give new meaning to the life of a young delinquent. 

In the novel’s now time, Pluto is dying. Erdrich’s story is a slice of American history — a chronicle of what was once called the frontier and how it developed, only to wither as the economy changed. The judge muses, “as I look at the town now, dwindling without grace, I think how strange that lives were lost in its formation. It is the same with all desperate enterprises that involve boundaries we place upon the Earth… we seem to think we have mastered something. What? The Earth swallows and absorbs even those who managed to form a country, a reservation. (Yet there is something to the love and knowledge of the land and its relationship to dreams — that’s what the old people had. That’s why as a tribe we exist to the present.)” (p. 115)

The subliminal text of Erdrich’s narrative testifies not only to the survival of Native Americans despite the odds but also to the rich cultural input that the United States lost when their society was, at worst, eradicated and, at best, sidelined in order to found a new “white” country. 

Though many events in this story are tragic, the overall effect is quite life affirming, mainly because of the numerous characters who throw themselves into life so bravely, so resourcefully — and they persist. While the past cannot be changed, people can live with it; some learn its lessons and change, many of them for the better.

MIAMI — A mysterious and sometimes fatal brain disease that has afflicted children in northeastern India for years could be linked to a toxic substance in litchi fruits, US researchers said Thursday.

Investigators say more research is needed to uncover the cause of the illness, which leads to seizures, altered mental state and death in more than a third of cases.

In the meantime, doctors who encounter sick children should takes steps to rapidly correct low blood sugar, which can make the disease more likely to be fatal, said the report by the US Centres for Disease Control and Prevention.

The outbreaks have coincided with the month-long litchi harvesting season in and around the Muzaffarpur district of Bihar state since 1995, said the CDC’s Morbidity and Mortality Weekly Report.

In 2013, some 133 children were admitted to local hospitals with seizures and neurological symptoms.

Most were aged one to five, and nearly half (44 per cent) of them died. Those who died were more than twice as likely as other patients to have been admitted to the hospital with low blood sugar, known as hypoglycemia.

Tests on the spinal fluid of patients came back negative for infectious agents like Japanese encephalitis virus, West Nile virus and other known pathogens in the area. 

A study that compared ill children to a control group in the area found that those who got sick were more than twice as likely to have spent time in orchards or agricultural fields.

These findings “raised concern for the possibility of a toxin-mediated illness,” said the CDC.

More study in 2014

From the end of May until mid-July last year, 390 children were admitted to the two referral hospitals in Muzaffarpur with illnesses that met the same case definition used in 2013.

“As in previous years, clustering of cases was not observed; the illness of each affected child appeared to be an isolated case in various villages,” said the CDC, noting that about 1,000 people lived in each village.

“The number of cases declined significantly after the onset of monsoon rains on June 21, 2014.”

Parents and caregivers said the children seemed healthy until they suddenly began experiencing convulsions, usually between 4am and 8am, followed by an altered mental state. Most did not have a fever on admission to the hospital.

Thirty-one per cent of the children died.

“The 2013 and 2014 Muzaffarpur investigations indicate that this outbreak illness is an acute noninflammatory encephalopathy,” said the CDC.

Component in seeds?

Researchers are carefully looking at a component found in litchi seeds known to cause hypoglycemia in animal studies.

Litchi fruits near the homes of affected children are being tested for the compound, known as methylenecyclopropylglycine (MCPG), and environmental samples are being taken from their homes and water supplies to search for pesticides.

Researchers think MCPG may cause severe hypoglycemia and illness much the same way as a similar toxin, hypoglycin A, which has caused “acute encephalopathy in the West Indies and West Africa after consumption of unripe ackee, a fruit in the same botanical family as litchi,” said the CDC.

Outbreaks of neurological illness have also been observed in litchi growing regions of Bangladesh and Vietnam, “raising further interest in a possible association between litchis and this illness”.

An investigation into the Bangladesh cases focused on pesticides used in litchi orchards, but found no specific culprit.

The Vietnam probe looked at “possible infectious agents that might be present seasonally near litchi fruit plantations but found none to explain the outbreak”, the CDC said.

Until researchers uncover the cause, parents are urged to seek immediate medical care for their children if they show symptoms, and doctors should promptly check for hypoglycemia and correct it as soon as possible.

SAN FRANCISCO — Microsoft’s HoloLens goggles have hit a sweet spot between Google Glass and virtual reality headgear, immersing users in a mesmerising world of augmented reality holograms.

The glasses, which the US technology titan sprang on an unsuspecting press recently, elicited descriptions such as “magical” and “unbelievable”, the first time in a while such praise was heaped on a Microsoft creation.

The augmented reality goggles are a step in a different direction from virtual reality headgear such as Oculus Rift and Sony’s Project Morpheus system, as well as Google Glass.

At private demos of HoloLens in a carefully guarded lower level of Microsoft’s campus in Redmond, Washington, cameras, recording devices and even smartphones were not permitted.

Microsoft executives said the holographic capabilities built into Windows 10 operating software — to be released late this year — would open doors for developers to augment tasks from complex surgery to motorcycle design.

In a captivating demonstration, a prototype HoloLens turned a room into the surface of Mars.

HoloLens wearers found themselves standing near a 3D representation of the Rover, free to roam Mars, at times accompanied by a NASA scientist projected into the scene and communicating through Skype.

“This is the future of space exploration,” said the scientist, represented by a glowing golden spacesuit reminiscent of vintage science fiction films.

NASA team members can use HoloLens to move about as if they are on Mars and figure out where they want the Rover to go and what they want it to do.

Work and play

Through a series of scenarios, HoloLens overlaid virtual scenes on real space, allowing wearers to safely and efficiently navigate rooms while engaging with 3D imagery using voice, gaze or gesture.

The head piece tracks eye movements, then lets wearers use a simple finger flick to interact with whatever they focus on.

Replacing a light switch became a collaborative effort, as one individual with a tablet computer guided the job, overlaying arrows or notes that floated in the air.

The room was then converted into an extension of the building block themed game Minecraft, with castles on floors and table tops. With voice commands and taps of the finger, a wearer built or destroyed, and sometimes vanquished zombies.

The Microsoft headgear even became a tool for designing virtual toys then made real using a 3D printer.

HoloLens also promises scintillating integration with video games, and Microsoft has a broad and devoted fan base for Xbox consoles.

The future of computing

“HoloLens offers a new platform and experience for computing on the scale of the original PC and the launch of Apple iPhone,” Forrester analyst Frank Gillett said in a blog post.

And Facebook co-founder Mark Zuckerberg has depicted virtual reality as a computing platform poised to succeed the mobile Internet era centred on smartphones and tablets.

He backed his belief by buying Oculus VR last year in a $2 billion deal.

Because virtual reality headgear disconnects users from their immediate surroundings, some people worry about what is happening in reality or what they might bump into.

“Virtual reality makes sense for gamers pretty much immediately,” said Endpoint Technologies analyst Roger Kay.

“I think augmented reality is actually how this type of technology is going to hit in to the general population.”

By contrast, Google Glass essentially displays a miniature version of a smartphone screen in an upper corner of one lens.

People can glance to see text messages, video or other scenes in small displays, and also take pictures or video, controlling the eyewear with voice commands or taps on frames.

Google recently ended sales of Glass through an Explorer programme, but a lower cost and more fashionable version is expected to make it to market.

“I have to say Microsoft has truly delivered a mixed reality experience that will delight,” Forrester analyst James McQuivey said in a blog post.

“It’s on everybody else — from Apple to Samsung, Oculus VR to Magic Leap — to match Microsoft’s opening bid.”

“Leave it till tomorrow to unpack my case, honey disconnect the phone,” sang Beatle Paul McCartney in 1968 in “Back in the USSR”, the opening song of the now legendary White Album. To have peace of mind for a short while all that they needed to disconnect back then was to pull out the cable of a simple analogue phone. How many devices and systems to disconnect today for peace of mind? Not to mention that actual disconnection (from the web) consists of more than a simple wire to unplug.

Comes a time when too much is too much. We may not be there yet but we’re surely approaching a situation where excessive web connection to IT networks is going to backfire.

The industry, understandably, wants you to connect every single object you own and use. It’s a vicious circle of the worst kind. By buying more connected devices we serve, willingly or unwillingly, as guinea pigs, as the perfect testing ground and lab for the industry that, therefore, can use our feedback and experience to improve the devices, only to inject more of them in the market. And all over again.

It makes sense to have a computer of a smartphone connected, but why should a spoon (yes a spoon…) be connected? It’s been almost two years since Hapilabs introduced the Hapispoon that can warn you if you eat too fast or too much and that can keep a record of your good or bad eating habits by sending the report over the web. “Another tool in a utensil drawer that won’t be used,” was one of the comments found on the web about the Hapispoon.

Many of the famous Japanese makers of wristwatches, with Seiko and Citizen in the lead, are now offering models that are connected to the Internet. These are not digital smartwatches that talk to your smartphone via Bluetooth but regular, often fancy and expensive wristwatches that rely on the connection to keep perfect time and date depending on where you live, where you are travelling, as well as your location’s daylight saving time. Not forgetting their ability at reading your GPS position.

It takes a little time to say whether a connected object is useful or ridiculous. Without enough time one does not have enough perspective to tell. Some cases, like the Hapispoon, however are obvious!

A web connected collar to locate your pet or a tiny device to locate your luggage in an airport can prove handy, but where do you set a limit?

Canadian innovator Hexoskin last year suggested a connected shirt that monitors your body and sends alerts about your health in specific cases. Readiymate goes further. The company proposes DIY kits that let you turn some objects into web connected ones, admitting they become merely toys — albeit connected ones.

At the 2015 edition of Los Angeles celebrated CES technology show, wearable web connected objects attracted huge audience.

“At the end of the day, what we’re creating is information,” says Ric Asselstine, CEO of Terepac Corp., a maker of microelectronics that are integrated into objects so as to make them smart. It may true but excessive amount of information precisely is the core issue today. The more information is generated and the higher the risk of hacking, of identity theft, and of plain theft of property and wealth. Not to mention that most of the time it is all but raw information, not having undergone any meaningful or useful analysis.

The sky is the limit goes the saying. When it comes to high-tech and web connectivity it is more outer space than just the sky. Soon we will want to scream “enough” and disconnect.

LONDON — Video-based therapy for families with babies at risk of autism improves infants’ engagement, attention and social behaviour, and might reduce their risk chances of developing the condition, the findings of a small scientific study show.

Researchers publishing the findings in The Lancet Psychiatry journal said they showed that using video feedback-based therapy to help parents understand and respond to their baby’s early communication style might help modify emerging autism symptoms.

“Targeting the earliest risk markers of autism, such as lack of attention or reduced social interest or engagement, during the first year of life may lessen the development of these symptoms later,” said Jonathan Green, a Manchester University professor of child and adolescent psychiatry, who led the study.

People with autism have varying levels of impairment across three areas: social interaction and understanding, repetitive behaviour and interests, and language and communication.

The exact causes of the neurodevelopmental disorder are not known, but evidence shows they are likely to include a range of genetic and environmental factors.

As many as one in 50 school-age children in the United States are diagnosed with autism, although some of these will be milder cases. In Europe, the rate is around one in 100 children.

“It will be important to document whether any such changes observed in the children’s behaviour persist in the absence of continued intervention,” said Melissa Allen, an autism specialist at the University of Lancaster.

SYDNEY — Australia faces a rise in temperature of potentially more than 5^oC by the end of the century, outpacing global warming worldwide, the country’s national science agency said on Tuesday.

In its most comprehensive analysis yet of the impacts of climate change, the Commonwealth Scientific and Industrial Research Organisation (CSIRO) painted a worst-case scenario of a rise of up to 5.1^oC by 2090 if there are no actions taken to cut greenhouse emissions.

“There is a very high confidence that hot days will become more frequent and hotter,” CSIRO principal research scientist Kevin Hennessy said. “We also have very high confidence that sea levels will rise, oceans will become more acidic, and snow depths will decline.”

The dire warning from the government-funded agency is at odds with the official line from Australian Prime Minister Tony Abbott, who in 2009 declared the science of climate change was “crap”.

Abbott last year scrapped a tax on carbon pricing and abolished the independent Climate Commission, saying recent severe droughts that have crippled cattle farmers were “not a new thing in Australia.”

As the host of the Group of 20 last year, he attempted to keep climate change off the agenda, resulting in an embarrassing backdown at the Leaders Summit in Brisbane after US President Barack Obama used a high-profile speech to warn Australia that its own Great Barrier Reef was in danger.

One of the world’s biggest carbon emitters per capita, Australia initially declined to join the United States, Japan, France and others in contributing to the United Nations’ Green Climate Fund.

At the Lima climate change conference in December, Australia announced it would provide A$200 million from its existing aid budget — a method of contributing that went against agreements when the fund was set up at the Copenhagen conference in 2009.

Abbott has committed A$2.55 billion ($2.21 billion) to a domestic initiative to reduce Australian’s emissions by 5 per cent below 2000 levels by 2020.

The new research by CSIRO and the Bureau of Meteorology, using some 40 global climate models, has Australia warming at a greater rate than the rest of the world.

The 5.1^oC projection for 2090 is at the top end of a range starting at 2.8 ^oC and is dependent on how deeply, if at all, greenhouse gas emissions are cut. The world average is for an increase of between 2.6^oC and 4.8^oC.

The report said the annual average temperature in Australia would likely be up to 1.3^oC warmer in 2030 than the average experienced between 1986 and 2005.

To compound our misery, my favourite supermarket right across the road from our house, has been bought over and the new owners have hiked up the prices of everything and anything in their store. 

Which is fine, I mean, how can I argue with their personal business decision? But what gets me mad, and continues to give me a steady rise in blood pressure is their manner of doing so. 

The consistent theme in this brand-new store is the total lack of customer care; the concept is not understood somehow. All their salespeople have the same mindset, and it is as if they are obliging us by providing the goods. The fact that we pay exorbitant amounts of money to procure them simply escapes their notice.

Where “consumer is always right” philosophy is not assured what can one expect but continual bad service? I will recount one incident for you, dear readers, and you can judge for yourself. 

A week ago I went there to buy some groceries and picked up a packet of lentils. The price tag read one figure but when I went to pay for it at the cash till, the machine announced four times the amount! For that one item! 

We could not believe our eyes, the lady cashier as well as me. She swiped the packet again, and the result was also the same: JD2 on the packet and JD8 on the tiny computer screen. 

After complaining to the storeowner, an irritable man on a wheelchair, he proceeded to explain the error. Apparently, the price of the commodity had been raised and recorded on the computer software but had simultaneously not been increased on the labels of the products. 

Now, whose fault was that? Why should the buyer be made to pay for this oversight on the part of the mismanaged shop? I lost my temper and got into a heated argument. After much quarrelling, my overcharged money was returned to me, so I went back somewhat placated. 

If it were any other country my entire shopping would have been compensated. Client wooing strategies were different there. But in this shop such pampering of the consumer was unheard of. If anything, they were ready to chase me off their grounds. 

By now, a seed of doubt had settled in my head, and I simply could not shake it off. Supposing I had not noticed this swindling and deception on my own, would I have been cheated time and again? Perhaps yes, but did the management care? I don’t think so. 

Yesterday, I went back again, to pick up a shampoo. The manager they had recently hired was rude, obnoxiously so. What was the problem, said the voice in my head? Why was he so disinclined towards being pleasant?

The purchase I made was once more wrongly marked. Actually, it was not even marked but was placed on a shelf where it was not supposed to be. And the rack where it belonged had other, latest versions of the brand, which were at a higher price. 

I figured that out, but since there was no price-sticker on it, I was made to wait while they went and manufactured a new one. The person-in-charge did not have an apology to offer. He just snatched the JD10 note from my hand. And then thrust the pack at me.

I just wish I had pushed the shopping trolley over his right foot. 

NEW YORK — A new wave of experimental cancer drugs that directly recruit the immune system’s powerful T cells are proving to be immensely effective weapons against tumours, potentially transforming the $100 billion global market for drugs that fight the disease.

But top oncology researchers are concerned about the two emerging technologies, citing dangers seen repeatedly in clinical trials including the potentially fatal buildup of toxic debris from killed tumour cells and damage to healthy tissue. Such side effects could block regulatory approval if they aren’t controlled, researchers and drug company executives said in interviews with Reuters.

In some trials, the two new approaches, known as CAR T cells and bispecific antibodies, have eliminated all traces of blood cancers in 40 to 90 per cent of patients who had no remaining options. The drugs could reap annual sales in the tens of billions of dollars for their manufacturers, especially if they can also eliminate solid tumours in such terminally ill patients.

CAR T cells, or chimeric antigen receptor T cells, are T cells that have been removed from the body and attached through genetic engineering to an antibody fragment that recognises a specific tumour protein. T cells are an especially powerful disease fighting kind of white blood cell. The result is a drug with the killing power of a greatly enhanced T cell, combined with the spotting-spotting ability of an antibody.

Bispecific antibodies are a twist on conventional antibodies, Y-shaped proteins whose two arms grasp for the same protein target found on cancer cells.

With bispecifics, one arm of the antibody typically grasps a cancer cell while the other arm takes hold of T cells, bringing the mortal enemies into contact. The T cell punches holes into the adjacent tumour cell and injects deadly enzymes. Conventional antibodies, by contrast, don’t directly recruit T cells.

“Unleashing the killing power of the T cell directly on the tumour cells allows a large increase in potency of these antibodies,” said Dr David Scheinberg, chairman of molecular pharmacology at Memorial Sloan Kettering Cancer Centre.

Investor excitement over these therapies have helped boost interest from companies including Amgen Inc. and Roche and have fuelled a jump in share prices of smaller firms such as Kite Pharma Inc., Juno Therapeutics and Bluebird Bio.

“We take patients that have failed every treatment, every chemo combination, that have just two to six months to live. You give them a CAR, and within three to four weeks you can see massive tumours melting away,” said Arie Belldegrun, chief executive officer of Kite. The company went public in June and announced a partnership with Amgen earlier this month.

CAR T cells could cost $300,000 to $500,000 per patient, if approved, making them among the world’s most expensive drugs and testing the ability of insurers to pay for them, said Les Funtleyder of E Squared Asset Management. The hedge fund owns shares of Kite Pharma. Bispecific antibodies could command prices of $200,000 or higher, he said.

The potency of the experimental drugs comes with some dangerous potential side effects. In the killing process, inflammatory chemicals from the medicines and the tumour cells, called cytokines, are released into the bloodstream and can cause fever, low blood pressure and rapid heartbeat that can be life threatening.

The drugs, because of their unique structure and how they work, make it harder to predict whether they will go astray, said Dr Bindu George, team leader of the US Food and Drug Administration’s Office of Cellular, Tissue and Gene Therapies, who called CAR T drugs perhaps the most interesting new technology.

Most CAR T cells and bispecific antibodies in development identify blood cancer cells by a specific protein, CD19, found on the surfaces of lymphomas and leukaemias. Because the same protein can also be found on non-cancerous cells, the drugs can go off track and attack healthy tissues.

“Our biggest concern would be an off-target toxicity that wasn’t expected and we didn’t know the cause of it,” George said. In that case, “we might have to ask [the drugmaker] for additional information, how the toxicity happened, what organ it was, and literally go back to the drawing board.”

Taming a powerful drug

Researchers have used anti-inflammation medications to tame some of the adverse reactions, not always successfully. A study of CAR T cell treatment sponsored by Juno for patients with aggressive non-Hodgkin’s lymphoma was briefly put on hold after two people died.

Unlike antibodies, which are excreted from the body within days or weeks, engineered CAR T cells are expected to circulate for years or even a lifetime in the bloodstream, potentially providing lasting benefits, but also risks.

“You can start to reject normal tissues; it can kill organs or cause autoimmune disease, and you don’t want that,” said Zelig Eshhar, a professor emeritus of the Weizmann Institute in Israel who pioneered the CAR approach.

To reduce that danger, researchers are attempting to build “suicide switches” into CAR T cells to turn them off after they have wiped out all signs of cancer.

At least 30 bispecific antibodies are believed to be in development, including ones from Roche, Johnson & Johnson, AbbVie and Eli Lilly.

A growing number of drugmakers are also racing to develop the first CAR T therapies, including Kite, Novartis, Juno, Cellectis and its partner Pfizer Inc., and Bluebird, in partnership with Celgene Corp.

Expensive option

The FDA in December approved the first bispecific, Amgen’s $178,000 Blincyto for acute lymphoblastic leukaemia (ALL) that did not respond to previous treatment. The cancer, prevalent in children, is diagnosed each year in an estimated 6,020 Americans, killing about a fourth of them.

One-third of patients in the Amgen study had no detectable cancer for nearly seven months after receiving the drug through a month-long infusion.

A main hope for Blincyto is that it will keep patients alive until they can receive stem cell transplants, their best chance of a possible cure.

CAR technology may also come to the rescue where few options remain.

“If doctors and specialists learn how to control this very powerful gun, CAR T cells could save hundreds of thousands of people in the United States,” said Ori Hershkowitz, a Tel Aviv-based fund manager with Sphera Funds, which owns shares of Kite and rival CARs developer Novartis.

A Novartis trial showed 27 of 30 children and adults with ALL had no signs of the disease after being treated with its CAR T drug. Some 78 per cent of patients were still alive six months after treatment, while some sustained remission for up to two years.

But everyone in the study developed cytokine release syndrome, including a severe form of it in 27 per cent of patients.

“It certainly needs to be watched and evaluated,” said Usman Azam, global head of cell therapies for Novartis. He still believes the drug’s benefits provide “compelling hope that you can potentially cure patients”.

Roche’s Genentech unit is conducting a mid-stage trial of a bispecific antibody to treat head and neck cancer and colorectal cancer. It is studying a dozen others in preclinical trials against cancer, Alzheimer’s disease and inflammatory diseases.

Paul Carter, a Genentech executive, was cautious about the prospects.

“It’s too early to say whether this will be a home run, although there’s optimism it will be at least a base hit that will help us figure out how to go further.”