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UCLA s Scott Layne on Lab Automation to Combat Infectious Diseases

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At A Glance

Name: Scott Layne

Position: Tenured Associate Professor, School of Public Health, University of California, Los Angeles

Background: Residency (internal medicine) and fellowship (infectious diseases), UCLA Department of Medicine — 1992-1996; Postdoc, Center for Nonlinear Studies, Los Alamos National Laboratory — 1982-1985; MD, Case Western Reserve University — 1976-1980

Having spent parts of his career as a physicist, medical doctor, and professor of public health, Scott Layne has developed an area of expertise — the role of laboratory automation in combating emerging infectious diseases or bioterrorism — that is at the crossroads of all three. In 1999, Layne organized the meeting “Automation in Threat Reduction and Infectious Disease Research Needs,” and has written a book on this topic. At this week’s Association for Laboratory Automation LabFusion conference in Boston, he is delivering a keynote speech on related topics. Inside Bioassays spoke with Layne prior to this presentation.

You have an interesting blend of medicine and physics in both your professional and educational experience. How did you become interested in your current area of expertise and how does it fit in with this background?

It was a bit of an evolutionary process. About 10 or 15 years ago, I was involved in doing basic virology research with AIDS and HIV. There is so much genetic variation in that virus that simply studying a few viruses — although there is value in that — it’s beyond human hands to understand what all the variations in the virus might be. So that’s really what got me started in thinking along these lines. And moving forward, it just became very clear that there were other problems in infectious disease, in addition to HIV, that were beyond human hands. That included other infectious agents such as flu and multi-[drug] resistant tuberculosis. And back in the late 1990s, I organized a meeting that was hosted by the Institute of Medicine and the National Academy of Engineering. [I helped] in putting together an advisory panel. It just became clear in going through that process that problems in biological terrorism were very important, as well — and this was all before 9-11. So this is how I started moving on this track of emerging infectious diseases and agents of biological terrorism.

One of the initiatives of this meeting was to build a network of high-throughput labs for the purpose of infectious disease research and bioterrorism response readiness. How is that initiative going?

It’s been four or five years since having the initial concept of bringing a group of people together to have this meeting. We don’t have a network of high-throughput laboratories yet, but I think two things have happened in the past five years. The technology has gotten even better, and I think there is a growing consensus that this sort of capability is needed. It somewhat flies in the face of the usual individual investigator-initiated science — kind of the typical R01 type of science that’s done in the NIH, and it involves a blend of engineering and science. There was a follow-up meeting after the 9-11 events and after the October events — the anthrax letter mailings — that was called by three national academies: The National Academy of Science, the Institute of Medicine, and the National Academy of Engineering. And they came out with a report that was published in 2002 called “Making the Nation Safer: The Role of Science and Technology in Countering Terrorism.” (http://www.nap.edu/html/stct/) And there was one chapter that focused specifically on biological threats. There were a number of recommendations in that chapter that pointed towards the need [for] high-throughput methodologies — either national or global networks — as well as an integrated national strategy and integrated approach to the problem. So all of this has been increasingly recognized and needed — I’d say the momentum is building. And I think the most recent outbreaks we’ve had of SARS and avian influenza in 2003 and 2004 in Southeast Asia [are] electrifying the need for all this. So the timing is right to move forward with this.

What are some top-of-mind examples of how these high-throughput automated labs can help in combating infectious disease or bioterrorism?

There are two parts to this question: One pertains to so-called naturally occurring infectious disease, and one relates to acts of biological terrorism. The emerging infectious disease [problem] is that an outbreak can pop up at any time. Let me use flu as an example. We have an extensive surveillance system throughout the world for flu that collects, perhaps, 200,000 to 300,000 samples. The number of samples, though, that is finally analyzed in great detail is surprisingly small — maybe on the order of 5,000. And on top of that, there’s a time delay between the sample being collected and the analyses being done. So compared to manual methods, what a high-throughput laboratory will do is enable many more samples — tens, hundreds, or even thousands more samples — to be analyzed comprehensively. And the time delay in analyzing them could be shrunk down to just a matter of days. So it will increase, if you like, the bandwidth and the speed with which we look at infectious disease outbreaks. And from a public health perspective, there’s no doubt that people in high levels of government are going to have to make monumental decisions regarding naturally occurring infectious disease outbreaks. This would enable such decisions to be made with far more comprehensive information.

From the point of view of biological terrorism, I guess one has to look at this in four phases: Prevention, deterrence, response, and response. One response is the public health response, and another response is that national security response, and prevention and deterrence speak for themselves. There’s a short list of bio-threat agents that are the most likely ones to be used in an act of terrorism. The anthrax letters that got sent out in October of 2001 — as far as I know, we really just don’t know what their origin was. So there are really two roles here for high-throughput labs. One is doing upfront forensics on samples, and ascribing the fingerprints, or molecular fingerprints, or molecular characteristics of agents to their origins. And a database that contains that information is only as good as the number of data points that we have. Over time, what these labs would enable is the building up of a complete or comprehensive database on particular biothreat agents. Once an outbreak occurs or attack happens, then there’s going to be the need to process tens to hundreds of thousands of samples, so surge capacity [is important] — laboratory and informatics surge capacity. The surge capacity can very easily overwhelm manual labs in the current system that we have. So the addition of a small network of high-throughput laboratories would enable us to accommodate a much larger surge capacity in a time of need.

You said earlier that the technology for this type of initiative has gotten better. What are some examples of that?

The world is much more linked than ever before. Now, up in the sky, we have satellites that enable global positioning. And so now, [we have] the ability to go out with something as simple as a hand-held device — if you’re going to collect a sample — that would automatically tell you where you’re located. For example, it would have a bar code reader associated with it, and a sample would be collected, and an outbreak questionnaire with some really simple questions would be filled out. That sort of everyday, simple, off-the-shelf gadgetry did not exist five or ten years ago.

From a laboratory perspective, the other element to this is what I’ll call virtual warehousing. Services like FedEx, UPS, Airborne Express, or any shipping services now connect us globally, and so material samples can be moved around the world literally overnight.

A third element is in the gadgetry itself, in the high-throughput laboratory equipment and the methodology. At this upcoming LabFusion meeting, I don’t know how many vendors are going to be showing their equipment, but I know that in past ALA meetings, the number of vendors showing hardware has ranged from over 150 to maybe 200. So the smorgasbord of available boxes that can do just about anything you want to do in the laboratory is now available. For example, things that will allow samples to be input and output, liquid handling stations, thermocyclers, barcode printers and readers, plate sealers, incubators, sequencers, automated flow cytometers, automated storage devices for samples, and this is not a comprehensive list — it goes on and on. That sort of gadgetry did not exist even five or ten years ago.

The other element is laboratory standards. The American Society for Testing and Materials has an interconnect standard, as an example, called LECIS, the Laboratory Equipment Control Interface Specification. That is a pretty broad standard for being able to interconnect laboratory hardware into a system. And increasingly, these types of standards that will allow equipment to be connected between vendors are becoming adopted and recognized as important. And since these standards exist, the types of operating systems can now be created that are compliant with the standards. So mixing and matching very powerful equipment from vendors now becomes a possibility.

And on top of all of this, we now also have very fast computers and large storage devices, so it now becomes conceivable to be able to store terabytes to gigabytes of data, and to manage these economically. And then to have computers that are operating on the order of 10(14), or beyond, floating point calculations per second, along with algorithms that are efficient and can align sequences, search sequences, compare enormous numbers of data points against each other — data mining capabilities are just unprecedented. All of these elements together enable us to move forward.

 

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