Computer chip that detects new types of virus
Saturday, 15 November 2008
Syed Fattahul Alim
There was a time when scientists in the field of medicine had to work alone with their microscopes poring over the samples of blood, saliva or any other parts of the infected organ of a human body to identify the parasite or bacteria ailing the subject in question. For virus attack, the microscopes, however, were of little help. The job of the medical scientists of the past was really tiresome and boring as they had to remain glued to their chair for hours and working on the same samples for days, weeks, months and even years together. Before the invention of microscope, one can imagine how hard it was for the medical scientists to pursue their researches. To say that their task was hard is to take their effort too lightly. In fact their endeavour was not only hard, it was risky, too. One also reads of scientists of yore, who would think nothing of inflicting suffering on their own person or on members of their families just to test the effect of a drug or samples having the potential to cause disease or even death.
Those were the times of great scientists and also of great challenges and adventures. This is, however, not to say that today's scientists are not as dedicated as their predecessors were. Yes, there are certainly great scientists working in the different laboratories and scientific foundations even today. But there is a catch here. If truth be told, the survival rate of the scientists, more particularly, the medical scientist, of the past was lower than that of today. Reason for this, too, is obvious. For in those days, people who were especially gifted and who had the stamina to weather the indifference or even hostility of society towards them could hope to continue with their passion for scientific pursuit. And to add to their woes, they had to fend for themselves, without any support from any research establishment. Obviously, there was little possibility that people who were not really crazy about their pursuit would survive the condition of life for scientists in those days. Simply put, people with passion for their pursuit and who stood head and shoulders above their peers could only hope to tell the tale.
However, modern researchers are spared that kind of social indifference or lack of support. What is more, they have the scientific tools and kits to help them avoid the kind of boredom or risks their predecessors were exposed to. Consider the problem of finding out the virus a certain type of physical syndrome or disease is responsible for. Firstly, there is the problem of looking at a virus, which is so small that even modern electronic microscopes can hardly trace them. Now consider the awesome task of sifting through thousands of gene samples, which have to be matched with a gene belonging to a freshly discovered bacteria or virus. Unaided by latest tool in medical research like Virochip, as invented by Dr. Joseph DeRisi, the task would really be a formidable one.
Claudia Dreifus of New York Times tells below how that miracle was achieved through a discussion with the inventor himself.
"Joseph DeRisi's mantelpiece is heavy with awards and prizes. At age 39, Dr. DeRisi, a molecular biologist and biochemist, is a Howard Hughes Medical Investigator; a McArthur "Genius" Fellow; a professor at the University of California, San Francisco; and a winner of this year's prestigious Heinz Award for Technology, the Economy and Employment. Among his achievements is helping to invent the ViroChip, which greatly accelerates the ability of researchers to diagnose viral infections. An edited version of a two-hour conversation follows.
Q. How did the idea for the virochip first come to you?
A. My colleague Dave Wang and I were sitting around the office one day in 2000 asking, "How were viruses discovered in the past?"
We knew that it had always been a laborious and time-consuming effort. When an epidemic struck, what researchers generally did was go to electron microscopes and try to figure out what they were seeing. Sometimes, it took 10, 20 years to find a virus they knew had to be in there.
Earlier, when I was a Stanford graduate student, I'd worked on developing DNA microarrays, which are often called DNA chips. They allow a researcher to do many biological tests at once. The chips are now widely used in gene discovery, cancer detection, drug discovery and toxicology. So Dave and I reasoned that these DNA microarrays would be perfect for viral discovery. I said, "We can build a similar device representing every virus ever discovered, and it could simultaneously look for them."
Q. And you did build it. What does your virochip look like?
A. It's a glass slide onto which we've printed little DNA fragments of every virus ever discovered - about 22,000 different viral sequences. I designed the robot that made the chip. I then built that robot and wrote all the software to automate it. I've always been a serious computer nerd, as well as a biologist. Now is really the right moment for a scientist with that combination of interests. The way the chip works is this: If we are looking at a virus and trying to figure out what it is, we take some DNA and some RNA from a patient and we tag it with a fluorescent dye. Then we put that material onto the virus chip. Because matching genetic sequences stick to each other - the double helix - if there's a match between what's on the chip and our biological sample, a particular spot on the chip will glow. That tells us which virus the sample is. And, thanks to computers, we can do this with thousands of viruses at one time.
Q. Can your chip find undiscovered viruses?
A. It can. The ability to do it relies on evolution. It turns out that viruses evolve from each other, like everything else. So if you look at the evolutionary tree of viruses, you can find parts of their genome that haven't changed over evolutionary time. You can recognize what may be a new virus by identifying this little piece of their genome that hasn't changed and is represented on the chip.
Q. Is that what you did in 2003 with Sars?
A. Yeah. We had just finished building the full version of our ViroChip, when we read about SARS in the newspapers. We literarily begged the C.D.C. to send us samples of the virus. Once we had it, we immediately put it onto a chip. In less than 24 hours we confirmed that this was a novel coronavirus. We confirmed the ViroChip's finding by subsequently sequencing this virus's genome. This had never in history happened before. It was unthinkable five years earlier.
From now on, I don't think there is going to be any new viral epidemic that we will not be able to identify within a few days. It doesn't mean you'll find a cure right away. But you will be able to separate people who have it from those who don't. You can stop it from spreading, if you have a diagnostic. That's what got SARS under control.
Q. I understand that your chip has been helpful in diagnosing some avian viruses. Is that true?
A. After SARS, we got calls from veterinarians in Israel and Florida who told us that parrots, macaws and cockatiels were dying from this wasting disease, which they suspected was viral. Once we got tissue samples, the ViroChip quickly picked up that this was a bornavirus, something seen in livestock, but that hadn't been identified in birds before.
As with SARS, once we had a diagnostic tool, you could separate the sick birds from the healthy ones. You might not be able to save an infected bird, but you can certainly stop the epidemic from going any further.
Q. Are you using the same technology to study malaria?
A. Yes, we use DNA microarrays that are similar to the virus chips. Malaria is a one-cell parasite; it's not a virus. We built a chip that represents that organism's genome - 6,000 genes. And we grew large amounts of the parasite in vats of human blood. We were then able to use the chip to understand what genetic program these parasites run at the moment they infect human blood cells. This is important because all the clinical symptoms of malaria occur when the parasite infects a person's blood cells. This knowledge will assist drug and vaccine development.
Before we did this, it was anyone's guess which of the 6,000 genes were important. Now this data has gone to every malaria lab in the world, and they are picking specific genes to work on, many times based on our data. That's just amazing!
Q. Have you patented your virochip?
A. My colleagues and I considered it. But in the end, we saw no value in doing that. We want people to use this technology. By disseminating the technology freely, more researchers can utilize it faster. And that can produce more rapid advances in human health. We put the specifications into the public domain.
Q. You've just won the Heinz award. What do you plan to do with the $250,000 prize money?
A. I intend to use a percentage for special research projects on infectious disease, and I'll give a percentage to field operations working against malaria. After that, I'll pay my two young daughters' day care bills and also set up college funds for them.
I did my undergraduate work at the University of California when it was still affordable. But tuition keeps on rising. We'd better start saving now.
There was a time when scientists in the field of medicine had to work alone with their microscopes poring over the samples of blood, saliva or any other parts of the infected organ of a human body to identify the parasite or bacteria ailing the subject in question. For virus attack, the microscopes, however, were of little help. The job of the medical scientists of the past was really tiresome and boring as they had to remain glued to their chair for hours and working on the same samples for days, weeks, months and even years together. Before the invention of microscope, one can imagine how hard it was for the medical scientists to pursue their researches. To say that their task was hard is to take their effort too lightly. In fact their endeavour was not only hard, it was risky, too. One also reads of scientists of yore, who would think nothing of inflicting suffering on their own person or on members of their families just to test the effect of a drug or samples having the potential to cause disease or even death.
Those were the times of great scientists and also of great challenges and adventures. This is, however, not to say that today's scientists are not as dedicated as their predecessors were. Yes, there are certainly great scientists working in the different laboratories and scientific foundations even today. But there is a catch here. If truth be told, the survival rate of the scientists, more particularly, the medical scientist, of the past was lower than that of today. Reason for this, too, is obvious. For in those days, people who were especially gifted and who had the stamina to weather the indifference or even hostility of society towards them could hope to continue with their passion for scientific pursuit. And to add to their woes, they had to fend for themselves, without any support from any research establishment. Obviously, there was little possibility that people who were not really crazy about their pursuit would survive the condition of life for scientists in those days. Simply put, people with passion for their pursuit and who stood head and shoulders above their peers could only hope to tell the tale.
However, modern researchers are spared that kind of social indifference or lack of support. What is more, they have the scientific tools and kits to help them avoid the kind of boredom or risks their predecessors were exposed to. Consider the problem of finding out the virus a certain type of physical syndrome or disease is responsible for. Firstly, there is the problem of looking at a virus, which is so small that even modern electronic microscopes can hardly trace them. Now consider the awesome task of sifting through thousands of gene samples, which have to be matched with a gene belonging to a freshly discovered bacteria or virus. Unaided by latest tool in medical research like Virochip, as invented by Dr. Joseph DeRisi, the task would really be a formidable one.
Claudia Dreifus of New York Times tells below how that miracle was achieved through a discussion with the inventor himself.
"Joseph DeRisi's mantelpiece is heavy with awards and prizes. At age 39, Dr. DeRisi, a molecular biologist and biochemist, is a Howard Hughes Medical Investigator; a McArthur "Genius" Fellow; a professor at the University of California, San Francisco; and a winner of this year's prestigious Heinz Award for Technology, the Economy and Employment. Among his achievements is helping to invent the ViroChip, which greatly accelerates the ability of researchers to diagnose viral infections. An edited version of a two-hour conversation follows.
Q. How did the idea for the virochip first come to you?
A. My colleague Dave Wang and I were sitting around the office one day in 2000 asking, "How were viruses discovered in the past?"
We knew that it had always been a laborious and time-consuming effort. When an epidemic struck, what researchers generally did was go to electron microscopes and try to figure out what they were seeing. Sometimes, it took 10, 20 years to find a virus they knew had to be in there.
Earlier, when I was a Stanford graduate student, I'd worked on developing DNA microarrays, which are often called DNA chips. They allow a researcher to do many biological tests at once. The chips are now widely used in gene discovery, cancer detection, drug discovery and toxicology. So Dave and I reasoned that these DNA microarrays would be perfect for viral discovery. I said, "We can build a similar device representing every virus ever discovered, and it could simultaneously look for them."
Q. And you did build it. What does your virochip look like?
A. It's a glass slide onto which we've printed little DNA fragments of every virus ever discovered - about 22,000 different viral sequences. I designed the robot that made the chip. I then built that robot and wrote all the software to automate it. I've always been a serious computer nerd, as well as a biologist. Now is really the right moment for a scientist with that combination of interests. The way the chip works is this: If we are looking at a virus and trying to figure out what it is, we take some DNA and some RNA from a patient and we tag it with a fluorescent dye. Then we put that material onto the virus chip. Because matching genetic sequences stick to each other - the double helix - if there's a match between what's on the chip and our biological sample, a particular spot on the chip will glow. That tells us which virus the sample is. And, thanks to computers, we can do this with thousands of viruses at one time.
Q. Can your chip find undiscovered viruses?
A. It can. The ability to do it relies on evolution. It turns out that viruses evolve from each other, like everything else. So if you look at the evolutionary tree of viruses, you can find parts of their genome that haven't changed over evolutionary time. You can recognize what may be a new virus by identifying this little piece of their genome that hasn't changed and is represented on the chip.
Q. Is that what you did in 2003 with Sars?
A. Yeah. We had just finished building the full version of our ViroChip, when we read about SARS in the newspapers. We literarily begged the C.D.C. to send us samples of the virus. Once we had it, we immediately put it onto a chip. In less than 24 hours we confirmed that this was a novel coronavirus. We confirmed the ViroChip's finding by subsequently sequencing this virus's genome. This had never in history happened before. It was unthinkable five years earlier.
From now on, I don't think there is going to be any new viral epidemic that we will not be able to identify within a few days. It doesn't mean you'll find a cure right away. But you will be able to separate people who have it from those who don't. You can stop it from spreading, if you have a diagnostic. That's what got SARS under control.
Q. I understand that your chip has been helpful in diagnosing some avian viruses. Is that true?
A. After SARS, we got calls from veterinarians in Israel and Florida who told us that parrots, macaws and cockatiels were dying from this wasting disease, which they suspected was viral. Once we got tissue samples, the ViroChip quickly picked up that this was a bornavirus, something seen in livestock, but that hadn't been identified in birds before.
As with SARS, once we had a diagnostic tool, you could separate the sick birds from the healthy ones. You might not be able to save an infected bird, but you can certainly stop the epidemic from going any further.
Q. Are you using the same technology to study malaria?
A. Yes, we use DNA microarrays that are similar to the virus chips. Malaria is a one-cell parasite; it's not a virus. We built a chip that represents that organism's genome - 6,000 genes. And we grew large amounts of the parasite in vats of human blood. We were then able to use the chip to understand what genetic program these parasites run at the moment they infect human blood cells. This is important because all the clinical symptoms of malaria occur when the parasite infects a person's blood cells. This knowledge will assist drug and vaccine development.
Before we did this, it was anyone's guess which of the 6,000 genes were important. Now this data has gone to every malaria lab in the world, and they are picking specific genes to work on, many times based on our data. That's just amazing!
Q. Have you patented your virochip?
A. My colleagues and I considered it. But in the end, we saw no value in doing that. We want people to use this technology. By disseminating the technology freely, more researchers can utilize it faster. And that can produce more rapid advances in human health. We put the specifications into the public domain.
Q. You've just won the Heinz award. What do you plan to do with the $250,000 prize money?
A. I intend to use a percentage for special research projects on infectious disease, and I'll give a percentage to field operations working against malaria. After that, I'll pay my two young daughters' day care bills and also set up college funds for them.
I did my undergraduate work at the University of California when it was still affordable. But tuition keeps on rising. We'd better start saving now.