Every Second Counts Veredus Reduces Time Needed to Diagnose Disease
This year's gold winner offers a glimpse of a world where we don't need to wait days to know whether we have malaria, or bird flu, or SARS, and where we can be diagnosed on the spot, whether it's at an airport, on the battlefield or in a remote village. Its name captures both the futuristic image and what it really is: a Lab on a Chip.
But that's getting ahead of the story. Rewind a few years when Veredus Laboratories Pte. Ltd., a small start-up in a nondescript office on the corner of Singapore's first Science Park estate, started developing diagnostic kits for malaria and dengue fever.
The kits contained an important innovation, one that forms the core of Veredus' achievement: reducing the time taken to diagnose whether a patient is infected from up to a week to two days or less.
"If you look at an infection," says Dr. Rosemary Tan, the CEO, "it is very difficult to detect the disease during early onset, because there are just not enough infectious agents to detect." That means waiting for at least five days for the disease to be visible and testable.
Veredus' trick? Instead of waiting for the body to produce antibodies to fight the virus, it looked for the first messages the body gives off that it is under attack. These come from the virus' genetic material, or DNA (or single-stranded RNA, the messengers between the DNA inside the nucleus and the rest of the cell) that, when detected, will indicate the presence of an infection. Focusing on the genetic material of the virus reduces the wait for any infection to be spotted. In short: "I do not look for the response, I look for the virus," says Dr. Tan.
Another innovative step is required to generate workable amounts of DNA. This means using a process called Polymerase Chain Reaction, or PCR. While tiny quantities of DNA in theory contain all the genetic code we need to know about the owner, there may not be enough material to actually work with -- in forensic cases, for example, where the DNA is extracted from a very small sample.
PCR takes as little as one molecule of DNA and can multiply it millions of times until there's enough to work with. First, though, since PCR won't work with RNA, the RNA needs to be converted into DNA, the double-stranded molecules that contain the code for our genetic makeup, through a process called reverse transcription.
Once the DNA is created, then Veredus sends in its agents, called primers, to look for specific sequences in the viral gene that need to be amplified, a bit like looking for a specific page in a very large book, and then magnifying it so it stands out from the rest of the book.
All this was well and good, but Dr. Tan and her colleagues only realized they were onto something big when they started developing tests for bird flu.
Although malaria and dengue fever are big problems in Asia, there was not the same sense of urgency as with SARS and bird flu. So how would their diagnostic kits perform for these more crucial challenges?
When she and her colleagues started sending test kits to diagnose for the deadly human H5N1 strain of bird flu to Vietnam and Malaysia in early 2004, the results were impressive. This was before the world had started to get nervous about the disease, and while the number of cases remained relatively low. "That was the first thing I knew, from the results from Vietnam and Malaysia. I knew I had a very good kit," she says.
The next step has been to convert the diagnostic kit to one that could be contained on a chip, where the whole process could be done with nothing more than a microscope slide with a chip no bigger than a fingernail, a couple of devices to read the chip and to perform the PCR multiplication, and a computer to control the process and read the data from.
Drop the sample from a swab onto one of four tiny holes on the chip, insert the chip into the reader and, after the process described above, the sample will be pushed onto what's called a micro array, where the DNA will be tested against whatever disease, strain or combination of diseases is being diagnosed. The results appear as a sort of microscopic light show, where a bank of probes lights up depending on the results. The process produces results within about an hour.
The Lab on a Chip should be available early next year, says Dr. Tan.
Dr. Tan herself is excited, but apprehensive. She knows that Veredus, and the industry, are on the brink of a new world. But there are bound to be doubts. "It's always the same, right?" she says. "I am sure when the first plane flew, how many people were afraid to take a plane. There's always a barrier." Her self-assurance returns. "But this thing is going to save a lot of lives," she says. "A lot."
Veredus：分秒必争
本年度的金奖获得者让我们不必再为确认是否患上疟疾、禽流感或是非典型肺炎(SARS)而等待数日，也让我们无论在机场、战场或是偏远的乡村都能进行现场诊断。它的名字很有点未来派的意味：芯片实验室(Lab on a Chip)。
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但这还只是一种展望。让我们先回过头去看看。几年前，Veredus Laboratories Pte. Ltd.在新加坡第一科学园一间普通的办公室中开始创业，开发疟疾和登革热诊断工具。
这套工具里有重要的创新，这也是Veredus的核心成就：将确认是否发生感染的时间从一周左右降低到两天甚至更短。
Veredus首席执行长Rosemary Tan说，如果要从感染情况来诊断，在疾病发作早期很难监测疾病，因为还没有足够的致病因子供监测。这意味着至少需要等上5天才能发现和监测疾病。
Veredus有什么诀窍呢？它不是等待人体产生抗体抵御病毒，而是寻找人体受到攻击时发出的第一个讯息。这个讯息来自病毒的基因材料，即DNA（或单链RNA）：如果检测到这些物质，就说明存在感染。将重心放在病毒的基因材料上能够减少监测感染的时间。简而言之，用Tan的话讲就是：我不是寻找反应，而是寻找病毒。
还需要有一个创新手段来产生足够数量的DNA。这意味着要采用一种叫做聚合链反应(Polymerase Chain Reaction)的过程。尽管在理论上讲，数量很少的DNA就包含了所有者的全部基因代码，但在实践中材料数量太少可能就无法进行化验，比如在法医现场可能需要从非常小的样本中提取DNA。
而PCR可以将只有一个分子的DNA扩大数百万倍，使其能够提供有效信息。不过，由于PCR不能处理RNA，因此首先要将RNA转化为双链的DNA。
在产生DNA后，Veredus就会加入试剂，在基因中寻找需要放大的具体序列，这有点像从一本巨着中寻找特定的一页，然后放大它，让它脱颍而出。
Tan和她的同事是在开始开发禽流感诊断方法时才意识到责任之重大的。
尽管疟疾和登革热也是亚洲常见的主要疾病，但毕竟不像非典型肺炎和禽流感给人们那么强烈的紧迫感。那么他们的诊断工具在这些重大挑战面前表现如何呢？
当她和她的同事2004年初向越南和马来西亚提供诊断致命H5N1禽流感病菌的测试工具时，其结果给人们留下了深刻印象。当时禽流感还没有让世界感到紧张，而且感染的人数还不是很多。她说，我从来自越南和马来西亚的结果中了解了第一手资料。我知道我有了很好的工具。
下一步是将诊断工具集成到一个芯片上。这样化验过程只需要一个显微镜载片和指甲盖大小的芯片、读取芯片和进行PCR繁殖的装置、以及控制整个过程和读取数据的电脑就能完成。大约在一个小时之内就能得出化验结果。
Tan说，芯片实验室明年初就能投入使用。
Tan非常兴奋，但她仍保持着清醒。她清楚Veredus以及这个行业正在开拓一个全新的世界。不过当然也会有怀疑。她说，“事情不都是这样吗？相信第一架飞机开始飞行时，很多人都不敢坐。什么事开始都会有障碍。”她恢复了自信。她说，这将拯救许多、许多人的生命。
Jeremy Wagstaff
