This article was taken from the November 2011 issue of Wired magazine. Be the first to read Wired's articles in print before they're posted online, and get your hands on loads of additional content by subscribing online.
On December 26 2001 an electrical engineer called Christofer Toumazou rushed to see his nine-year-old son Marcus, who had just been taken to hospital. Marcus's kidneys had failed. When Toumazou arrived, Marcus was already on dialysis, connected to a machine that removed excess water and waste from his blood through a catheter in his abdomen. Later, it was found that Marcus suffered from a rare genetic disease that had progressively destroyed his kidneys. Without a transplant, he would have to undergo dialysis every single day to survive.
From that day, after school, from 6pm to 9am, Marcus had to lie on his bed and connect the catheter in his abdomen to a dialysis machine beside his bed. Controlled by a timer, the machine would pump about two litres of saline solution into his abdomen and, at a pre-set time, say four hours later, it would flush the solution out and inject another two litres of saline. Marcus's parents would wake him four times every night, take his temperature and blood pressure and weigh him. At the end of the week, they would take the measurements to the renal consultant at Great Ormond Street Hospital in London, who would analyse them and adjust the timer, the volume of saline and the medication dosage for the week ahead. "It was driving me bonkers, the rigmarole of disinfecting everything, taking the temperature, measuring the blood pressure,"
Toumazou recalls. "And if his levels were too high or too low, we would panic. I was obviously very emotional but, my God, I couldn't believe that my son was being kept alive by a technology that was so dumb and primitive."
At the time, Toumazou was a professor at the Department of Bioengineering at Imperial College London, with a growing reputation in the field of analogue semiconductor microchips. He had invented the world's first mobile phone that used both analogue and digital signals, and he had done work for companies such as Panasonic and Ericsson. By then, he had already started applying the technology of analogue semiconductor microchips to human health, making the first fully implantable cochlear implant for a company called Epic Biosonics. "They had an implant with a big battery and whacking wires. I reduced the battery and the processor to a tiny microchip that sat on top of the electrodes inside the ear," says Toumazou. That invention had also made him realise something that would transform him into one of the leading technology innovators in healthcare: that the microchip technology used in mobile phones was all he needed to change medicine radically.
When his son Marcus fell ill, the doctor compared his son's condition to Toumazou to having the engine of a Mini running a Rolls-Royce. "I almost fell over. I just thought, why didn't we manage the situation when he was younger and had the engine of a Mini running an actual Mini? He could have had done a genetic test and avoided reaching this state. But where was that test?"
Shortly afterwards, Toumazou went to see the rector of Imperial College, Richard Sykes, a biochemist who had been the executive chairman of pharmaceutical giant GlaxoSmithKline. Toumazou wanted to create a new institute and hire the smartest electrical engineers, biologists and medical doctors. They would invent genetic tests, continuous monitors and intelligent treatments for clinical illnesses by applying the technology of analogue microchips to human health. Toumazou raised £10 million, which Sykes matched with £12 million from the university, and in July 2007 the new Institute of Biomedical Engineering was opened by the Queen. Marcus, who had undergone a kidney transplant and no longer required dialysis, attended the ceremony and had a long conversation with the Queen. He told her how his father was changing healthcare by making microchips for the human body.
Toumazou, now 50, is of Greek-Cypriot extraction, with greying temples and tanned skin. He is gregarious, energetic and affable.
When asked about the first time they met him, a number of his friends say that they "immediately hit it off". He grew up in a modest part of Chelthenham, where he failed his 11-plus exam. The 16-year-old Toumazou planned to join his father in the catering business. Instead, he took an Ordinary National Diploma in engineering and, later, an engineering degree at Oxford Polytechnic. In his finals, he scored the highest grade of the class and his supervisor urged him to do a PhD. By 33, he was already a professor at Imperial College London, and in 2008 he was elected a fellow of the Royal Society - his proudest scholarly achievement yet.
The Institute of Biomedical Engineering at Imperial College occupies four floors of a building in South Kensington. Toumazou runs the Centre for Bio-Inspired Technology, a part of the institute sponsored by Winston Wong, a Taiwanese businessman who runs Grace Semiconductor, a $1.63 billion (£1 billion) corporation.
The headquarters of DNA Electronics, one of the companies founded by Toumazou -- which makes a disposable gene test device called Genalysis -- is on the ground floor. Affixed to the wall of one of the labs is a schematic depiction of the labyrinthine connections within the microchip at the heart of this new product. "We are really proud of this," says Toumazou, showing a prototype of Genalysis. The 5mm-square microchip is attached to a cartridge, similar to a SIM card, which he inserts into a black, iPhone-sized device. "You put a sample of saliva on this microchip, and in 15 minutes it tells you if you have a particular DNA mutation. There will be a microchip for every drug and every infection, and this will allow you to choose a medication that is suitable to your genetic make-up or to find out if you have a particular infectious disease. We call it one microchip, one drug, one bug. To get this sort of information today you still need big machines and people in white coats in labs. You send your saliva sample to a lab and wait weeks for a response. We put all of that together on this microchip that gives you an answer in 15 minutes."
In the late 1990s, Toumazou spent a couple of months at the research group of an engineer called Carver Mead at the California Institute of Technology. Mead is considered a founding father of Silicon Valley, a scientist-philosopher who derived the empirical basis for Moore's Law and who has a propensity for making enigmatic statements such as, "Listen to the technology and find out what it's telling you." Toumazou had read all his works. "If there was a Nobel Prize for engineering, Carver would get it," he says.
At the time, Mead was also working on a concept called neuromorphic engineering, which he developed with the renowned physicist Richard Feyman in the 80s.Mead assembled teams of physicists, mathematicians, computer scientists and biologists, and scrutinised how animal brains computed and how the retina processed information. They made analogue microchips that mimicked the biological operations of the human nervous system. Mead wanted to make better computers by copying the process by which biology made brains. As he once said at a conference, "You may think houseflies are stupid, but not nearly as stupid as our computers. And they can do all that on a few milliwatts. What is it about the physics of goo in the brain of a fly that can do that? There's nothing about the physics of goo that works with ions and membranes that can't work with electrons and insulars. There is no reason that, if we understood what this absolutely fantastic, remarkable structure is doing, we can't learn from it and develop a computational paradigm, which is completely different from anything that we know or have even imagined."
For Toumazou, the crucial observation made by Mead was that electrons in semiconductors and ions in biological membranes obeyed similar laws. But unlike Mead, Toumazou isn't interested in making better computers. He wants to make humans healthier. His big idea is to use semiconductor microchips in the human body, to monitor, replace and repair our biology. Consider one of Toumazou's inventions, the artificial pancreas. The beta cells, located in the pancreas, make and produce insulin, the hormone that regulates blood-glucose levels. These fluctuate daily, depending mainly on how much you eat and exercise. To prevent extreme fluctuations, the beta cells release insulin continuously, depending on how much glucose is required.
In a Type 1 diabetic, however, the beta cells have been destroyed by the body's immune system. To replace the function of beta cells, a diabetic has to use an insulin pen with a needle, and a blood-glucose meter, and is now responsible for deciding how much insulin to inject and when to inject it. In other words, a biological process that has been optimised by evolution for hundreds of millions of years has to be replaced by an open-loop process that ultimately depends on the patient to manage and may lead to serious complications.
The way a diabetic has to manage the disease needs the sort of open-loop technology that Toumazou finds primitive. So he invented a microchip that exactly mimics the beta cells' chemical behaviour.
The microchip is used with a subcutaneous glucose sensor and communicates wirelessly with an implanted insulin pump in the abdomen. When glucose fluctuates outside the normal range, the beta-cell microchip sends a signal to the pump, which releases the right dose of insulin at the right time, The patient is taken out of the equation. The loop is closed again.
Soon after Marcus's illness, Toumazou hit on the idea of making a generic microprocessor for the human body that could receive biological information from an array of sensors, process that information and transmit it wirelessly to a computer. Toumazou called his microprocessor the Sensium, a portmanteau of "sensor" and "Pentium" -- a sly reference to Intel's famous and groundbreaking computer microchip. He designed it to resemble a simple sticking plaster, and it has a paper-thin battery and external sensors that measure ECG, heart rate, body temperature, respiration and exertion. Patients using the Sensium plaster can be discharged earlier from hospital; doctors can monitor their health remotely and continuously. If the patient's vital signs deteriorate, an alarm is triggered, and the doctors can act to prevent critical events such as heart attacks.
To make the Sensium plaster, Toumazou created a company called Toumaz Technologies and brought in Alison Burdett, a former student who had helped him develop the concept for the plaster. Toumaz had no money but it had a vision: to use the Sensium to get people out of hospital."We tried to raise money," Burdett recalls. "We were laughed at. People were saying, 'What the hell are you talking about? No one will want this.'" But then the mood changed.
Technology that could save millions in costs became a promising investment. In 2007, Toumaz had signed a $40million deal with US healthcare company, Cardinal Health, and was working with one of the world's largest computer manufacturers, Quanta Computer, to create a non-disposable version of the plaster for the Chinese market.
Toumazou likes to explain that the plaster is irrelevant if the data is not continuous, accessible and valuable. It's the data that keeps patients out of hospital. In a 2010 study in the journal Circulation, with 194,000 cardiac patients, Leslie Saxon, a cardiologist at the University of South California, analysed the effect that remote wireless heart-rate monitoring of implanted defibrillators had, against a control group. All the patients visited the clinic twice a year on average; those with a wireless monitor transmitted their data on average four times a month. Saxon found that the mortality rate nearly halved for the patients with monitors. This suggested that remotely collected data improves the odds that a worrying condition is identified early and prevented from becoming critical. "The problem is that the mentality is 'life or death'," Toumazou says. "There's no place for prevention, for personalised care, for making healthy people healthier. Once a NHS doctor said to me,
'Your plaster is not going to take off because you're trying to replace an ECG monitor, and whatever your sophistication of your plasters, it won't perform better than an ECG monitor.' I said,
'This is not replacing any technology. This is additional technology that costs very little and will allow you to monitor a patient constantly and let him walk about or even go home. A nurse can still record his vital signs, but this will detect deterioration that the nurse will surely miss and will stop patients from going into intensive care.' You know what the doctor said? 'Ah! Now I understand.'"
Toumazou believes that his creativity derives from a lack of solid education in mathematics and physics at an early age. During his PhD, he would sketch electronic devices and circuits, putting things together like a child playing with Lego. Problem-solving was never an option. Instead he would come up with solutions for problems that did not exist. That was how he dreamed up his most important invention: a semiconductor microchip that can read DNA.
The idea came after several attempts to measure physiological parameters like glucose in blood samples using microchips. One of Toumazou's students suggested they try to detect DNA. Toumazou didn't know much about DNA at the time. A DNA molecule is a very large sequence containing millions of smaller molecules called nucleotides. There are four types of nucleotides -- adenine, thymine, cytosine and guanine. The researchers put adenine on top of the microchip, then added a solution with thymine, because they react. "We had a shock," he recalls. Every time the enzyme connected the adenine with the thymine, an electrically charged ion would be released and detected by the semiconductor microchip. The reaction was strong enough to give an electrical current and switch on the semiconductor. "Within half an hour I wrote a paragraph describing the method and asked the patent officer at Imperial College what I should do. She said, submit it straightaway."
Toumazou developed the microchip so that it could detect DNA sequences and thus practise genotyping -- the detection of genetic variation in humans. Most such variations are known as single-nucleotide polymorphisms (SNPs), because they consist of a variation in only one of the nucleotides. SNPs dictate genetic differences within the same species, such as eye colour, predisposition to certain diseases, and the capacity to metabolise different drugs.
Consider the drug Warfarin, a blood thinner used to prevent clots and strokes. About a third of patients on Warfarin cannot metabolise it because of SNPs on two genes, CYP2C9 and VKORC1. The reaction to Warfarin among patients with such genes is the second biggest cause of hospitalisation for adverse drug reaction. In the US, the Food and Drug Administration (FDA) estimates that two million patients start taking the drug each year, and a significant percentage are hospitalised within six months with internal bleeding. A study published in April last year by the Mayo Clinic and Medco found that genetic testing could reduce these hospitalisations by 31 per cent.
By2008,Toumazou was seeking investors for his new company, DNA Electronics. He had developed the prototype of the disposable gene test device and brought in a former student, Leila Shepherd, as the chief technology officer. Thaksin Shinawatra, former prime minister of Thailand and a friend of Toumazou, invited him to meet his former scientific adviser, the geneticist Craig Venter. They met one evening at a dinner reception in Bangkok. Toumazou and Venter spent the evening talking. Toumazou showed his Sensium plaster to Venter and explained how he was combining semiconductors and DNA.
Venter was impressed and, according to Toumazou, replied, "That's what's missing in biology: the interface with the IT world. We have the software but we don't have the hardware. You've got something here."
Venter had come in with a Malaysian man called KT Lim. After dinner, Lim invited Toumazou for coffee. Lim was interested in DNA Electronics and persuaded Toumazou to fly to Kuala Lumpur the next day to meet a man called Derrik Khoo. Khoo is a former business journalist who once got into a car with Bill Gates and asked him why he had failed to sell a million copies of Windows 3.5. Gates jabbed a finger in Khoo's face and said, "I'll get there." "I've met some of the most clever and successful people in technology, and Chris is just like those tech giants," says Khoo. "He reminded me of Jim Clark [founder of Silicon Graphics and Netscape], because Jim was an academic and an entrepreneur, and also because Jim was working with this very smart young student, Marc Andreessen. I see a very similar partnership between Chris and Leila Shepherd."
When Toumazou met Khoo at Kuala Lumpur airport, he asked what Lim's line of business was. "Tan Sri KT Lim," said Khoo, "is the CEO of the Genting Group, which owns casinos and holiday resorts.
He funded Venter's synthetic biology work. He phoned me and said,
'I just met Professor Toumazou and we had a long talk about his startup. I believe in what he is doing. I want to invest in him.'"
Khoo runs a subsidiary of the Genting Group, the Asiatic Centre for Genome Technology, which worked with Venter's synthetic-biology company, Synthetic Genomics, to sequence the genomes of palm oil and jatropha, a biofuel. "I see Craig and Chris as complementary," says Lim. "When they do work together, I'm sure they'll make a big leap forward in DNA research."
Shortly after visiting DNA Electronics, Khoo called Jay Walker.
Walker, a prolific inventor and internet entrepreneur, has known Khoo and Lim for many years. "When someone from Asia tells someone from America to visit someone in London, it's usually a bit of a goose chase," Walker says. "But not this time. It really was an eye-opener. I came away and said to Derrik, 'Wow, this guy is not kidding around.' It's hard to argue that what he is doing isn't revolutionary. He is trying to bring together an interface between the biological and the electronic worlds. He's coding microchips that have a direct interface with the human body. That is a radical leap forward short of decoding the electrical wiring of the human brain."
Whoever obtains early patents in this field will have huge power, says Walker. "It is no different to the original wave of semiconductor patents that set down the fundamentals. The value of this kind of intellectual property is typically off the charts.
Chris has been under the radar but his work will come as a big surprise to the rest of the world."
The first Wireless Health conference was held last year in San Diego, California. It drew many of the top researchers in the field of health telemetry and personalised medicine. Toumazou was invited to give a keynote speech."Unlike many top engineers, Toumazou understands the medical world," says Eric Topol, another keynote speaker. Topol is a cardiologist and a geneticist who was named Doctor of the Decade by the Institute of Scientific Information and has known Toumazou for years. He is currently planning clinical trials of Genalysis at his Wireless Health Institute in San Diego, one of the few in the world that combines wireless technology and genomics. "The only other place I know that does that," he says, "is the Institute of Biomedical Engineering in London."
Also at the conference was Patrick Soon-Shiong. Soon-Shiong is a medical doctor who, in 2010, sold a drug company, Abraxis, for $2.9 billion and today has a fortune estimated at $4 billion, which makes him one of the world's most influential investors in healthcare. Soon-Shiong has an ambitious vision that parallels Toumazou's. Like Toumazou, Soon-Shiong wants to get patients out of hospitals and back to their homes. In this case, "smart" medical homes, where devices monitor them remotely, and automatically send their biometric data into the cloud. Soon-Shiong wants to turn these analogue signals into information that can be used to quantify medicine. In Los Angeles, he is already trialling a system of smart medical homes whereby 40,000 patients would be managed by nurses from a call centre. The scheme halved the number of hospitalisations.
After his talk, Soon-Shiong introduced himself to Toumazou. DNA Electronics had just signed two non-exclusive licences for its DNA semiconductor microchip with two of the biggest companies in genome sequencing, Ion Torrent and 454 Life Sciences. Soon-Shiong and Toumazou sat for two hours talking about Toumaz and all the other work that Toumazou was developing. "It was like I had known him for years," says Soon-Shiong. "One of first people I hired for the board of Abraxis in 2001 was Richard Sykes, and Richard told me,
'There's this guy in London that I want you to meet.' That guy was Chris."
Soon-Shiong invited Toumazou and his team for another meeting in Los Angeles to talk about DNA Electronics and the artificial pancreas. The Nobel laureate geneticist James Watson, one of the discoverers of the structure of DNA, was also present. Since that meeting, Toumaz has got US FDA approval for the Sensium plaster, and Soon-Shiong signed a deal with Toumaz worth $25 million. "Sometimes I find all of this quite spooky. That I'm a fellow of the Royal Society, and I have these companies, and I can't believe I'm inventing all this stuff and that it's actually making a difference. I mean, I'm embarrassed to admit that I didn't even do my A-levels. And yet, here I am."
Joao Medeiros is Wired's Start editor. He wrote about the Paris tech scene in 09.11
This article was originally published by WIRED UK
