"Here is a sample tube. You twiddle your swab in here and put the sample in it. You attach it to this tube here. All the reagents are self contained inside. You press the button, close the lid - and 45 minutes later it gives you an answer. 60 minutes later if it's reverse transcriptase. That's it. That's the technology, that's the skill level you need - and you put the test you want into that..."
Roger Breeze and Robert Carlson at "Life Science Trends Worth Watching" (Panel discussion) held March 3, 2011, in Washington, DC.
This conference focused on the increasingly important and transformative role that the life sciences will play in the 21st century and the expanding and evolving connections between advances in the life sciences and U.S. national security.
"For a hundred years or more, diagnosis has actually been all about the process. Now it's really all about the result. This particular machine you can link to a cell phone...so diagnosis now is actually a cell phone accessory - state of the art diagnostic detection, it's a cell phone accessory. So if you look at what's been going on with disease reporting - official, cumbersome, disease reporting systems, they have really been circumvented by cell phone based ones, ProMed, Health Map and all the rest of them, where people are providing all this information. Now, if you couple that cell phone (there are 6 billion of them in the world) with a very simple device which feeds in to the cell phone with a state of the art detection that you' transfer that equipment, for the first time it gives a person almost anywhere..the first person to turn up at the site of a problem, the ability to investigate, do a state of the art detection, and report the information in close to real time. So this has been happening all around us - mostly outside Government - happening in the private sector - which is why this is all so important. And people no longer have to be dependent on Government actually giving them access to reagents. You have got the reagent because you have got a sequence on the internet and you can actually do all this yourself."
YouTube video. Warmwell transcript begins at 18.36 mins:
"I want to talk about the basics: diagnostics, vaccination, technologies that have been around since Louis Pasteur. And I'm going to focus on agriculture, something I know something about, which happens to be about 14% of the US economy even though there's no one from agriculture on the list of attendees today which may tell you something.
The 1990s were a decade of rising anxiety among a small circle of people in the government stemming from the disclosure of the Soviet Union's offensive biological weapons programmes, the proliferation of biological weapons expertise and technologies to other countries that were unfriendly to the US, and there were numerous domestic and international terrorist incidents involving microbes and toxins.
But it took the terrorist attacks of 2001 to get the Congress to actually act to establish legislation that criminalised the possession and unauthorised use of certain microbes and toxins that were considered to be exceptionally dangerous threats to our national security.
Now the select agent list has 38 viruses, bacteria and fungi that infect humans, and 33 that infect livestock and poultry - and these agents are regulated by either DHHS or USDA or both in the case of zoonotic agents.
10 years ago most life scientists and public health professionals were probably very surprised by the idea that a group of pathogens was considered so dangerous that their possession and use had to be actually regulated and criminalised in the US, but this was by no mens a new concept for agriculture.
Of the 33 USDA select agents that affect livestock and poultry 5 cannot be used as tools to attack agriculture so I'm not going to talk about those - but the other 28 are all foreign animal diseases - that is, they're dangerous diseases of livestock and poultry that don't occur in the US or have never occurred in the US on a daily basis although they're huge problems in parts of the world where they do occur. And one of the things that many perhaps don't realise is that for decades, helping countries to respond to those diseases has been an important component of US foreign policy - particularly in the Americas for Foot and Mouth disease control which has been an enterprise that has been going for more than 60 years.
Agriculture has long been worried about agricultural disease, whether you call them "select agents" or not. In fact, when Abraham Lincoln established the Department of Agriculture in 1862, one of the reasons was to help prevent the introduction of these dangerous livestock diseases into the US, even though, of course, at the time, people had no idea of the causes of these agents because the first human or animal disease virus to be discovered - foot and mouth disease - wasn't actually discovered until 1896.
The main concerns at the time in 1862 and in that era were foot and mouth disease, rinderpest and contagious bovine pleural pneumonia - select infections.
These agents have long been regulated in terms of international trade in agriculture. They're regulated by a body called the International Office of Animal of Epizoonotics in Paris, which is an element of the World Trade Organisation. And the OIE establishes the scientific basis for proper regulation of trade internationally in animals and animal products so that countries can't use fake phyto-sanitary trade barriers as non tariff trade barriers to open trade in livestock. And from its early days the OIE used to maintain a list aid of dangerous animal diseases which provoked the most international regulation. And when the select agent list was put together in 2001, USDA actually basically just migrated the OIE list of pathogens from Paris to downtown D.C. to become the select agent list.
So, my point here is the idea of select agents in the hands of terrorists was nothing new to US agriculture in 2001. They'd been recognised as natural threats to agriculture for decades.
In fact, 2011 marks the 250th anniversary of the first veterinary school which was established in Lyon, France, after several devastating outbreaks of rinderpest which was long the world's most dangerous livestock disease - outbreaks which, in Europe, killed about 200 million cattle - most of the population of cattle in Europe at the time when it was introduced
Until 1956, the United States did not have a laboratory - in fact, this hemisphere didn't have a laboratory in which these select agents of livestock could be diagnosed. IN 1946 there was a huge outbreak of foot and mouth disease in Mexico. The only diagnostic capability was at a laboratory in England. Samples were sent on an ocean liner to England. By the time the results came back, 6 weeks later, it was self evident by the devastating spread of this epidemic all over the country that it was actually foot and mouth disease. The US got involved to help mexico to control this because livestock producers were tremendously concerned that the disease would come across the border.
We spent 200 million dollars at the time - 1946 - 1952 - which is into the billions in equivalent money today. It was a quasi-military operation that went on for 6 years. Sixteen people were killed in the control campaign - mostly by farmers who wanted to shoot the vets or people who were coming to inspect their farms and kill their livestock. Over a million cattle were slaughtered. The slaughter rate was so great that the US and Mexico had to adopt the radical technology of growing foot and mouth disease in the tongues of live cattle, killing those cattle and making that virus into vaccine which was then injected after chemical treatment. That's actually how it was controlled at the time.
So, we didn't have a laboratory that could deal with these infections until the Congress in 1956 established the Plum Island Animal Disease Center and the US laboratory for research and diagnosis of 26 of the 28 of the agricultural select agents. The other two, which are avian influenza and Newcastle Disease virus were later on established in Athens, Georgia and Ames, Iowa.
So, I was the Director at Plum Island from 1987 to 1995. I was the Director of the USDA Research Programme at Plum Island, not the diagnostic Lab, which belongs to the Animal Plant Health Inspection Service. Given that there are 28 select agents and other foreign diseases that are important that aren't classified as select agents, and limited research funds, the question that people always used to ask - which these days you'd call "risk assessment" - "What is the most important foreign animal disease or select agent infection for the United States?" and the answer is: "The next one that occurs here."
So, 20 years ago, when we were faced with the question of what were the current threats at the time and what were the emerging threats, probably the most significant conclusion in retrospect was that in terms of natural disease outbreaks from unintentional introductions, accidental introductions of disease into the country.
The problem about the threat was actually not the pathogens but it was the changes in agribusiness, public perception and public opinion that had rendered the standard epidemic control measures completely unacceptable.
Our role in research is not to set US policy about how these diseases are controlled. Our role in research, as other peoples in research, is to produce tools and technologies that provide options for policy makers to adopt the most appropriate technology for the time.
So lets just start off by saying, "Well what was and is the US policy, should these diseases be accidentally or deliberately introduced into the United States?"
Now that policy actually goes back to Dr Giovanni Lancisi who was the personal physician for Pope Clement in 1711 when rinderpest erupted into Europe and started killing all the cattle in Italy. He established the basis of veterinary response to these disease epidemics: the owners of sick cattle were obliged to report to the Government. If you didn't report - if you were a clergyman you were sent to the galleys, if you were not a clergyman you were hung, drawn and quartered. (So this comes back to something like the stringent requirements that George would want to impose. There's precedent enough for all failure to respond to surveillance..)
The infected farms were quarantined. All the animals on them were killed. The in-contact animals were killed - and they were burnt or covered in lime and buried in the ground - 1711, three hundred years ago.
And he kept on doing that until the outbreak stopped. It was as simple as that.
Now apart from aerial spraying of mosquitoes if it's an insect-borne disease, our response today is essentially the same as in 1711. It's not our policy to use vaccines before there is a disease introduction or to use vaccines if there is an introduction.
In fact, the US does not have manufacturing capability for any of these foreign animal disease vaccines.
20 years ago, we did not believe that these responses, which were the standard ones in the textbooks, would be supported by the American people in any significant epidemic involving mass slaughter of animals, millions of animals.
Unlike late medieval Italy, we have single farms in the United States with 300,000 animals on them. If you're going to shoot all of the, burn them and bury them that's going to be one hell of a pyre.
We have localities in this country where there's a million dairy cows within a five mile radius. If you quarantine those the question right away is "What are we going to do with those thousands of gallons of milk which are going to be produced until the animals are in the ground. What are you going to do? Pour it on the ground? Pour it on the drains? What would you actually do?"
Some of these select agents infect horses. Are you really going to see the federal Government seizing people's horses and shooting them - without really any signs. IS that likely? It didn't seem likely twenty odd years ago.
Now these very same responses would actually exaggerate a deliberate biological attack, were one to occur as the result of a biological warfare incident- although that's probably very unlikely today.
As far as agricultural bio terrorism is concerned, I've come to believe over time that it's only the way we've chosen to respond to these natural disease outbreaks in the past that allows terrorists to threaten us with them in the future.
If we didn't have this theatre of mass slaughter and burning and burial on the tv news every night, there really wouldn't be any point in a biological attack on agriculture. It would be completely irrelevant.
We could have a whole separate meeting on agricultural threats but in the interests of time I'm just going to focus on the disease diagnostics and vaccines.
Many of these agricultural select agents are infectious; they spread quickly through an infected herd and spread quickly between farms and States with the movement of animals and animal products.
A single pig, infected with foot and mouth disease, coughs and splutters up enough virus in a single day to infect a hundred million cattle. This is a huge amount. If you have a state where you have 20 million pigs, that's an awful lot of virus produced on a daily basis and spread as an aerosol cloud.
We are uniquely vulnerable because of the structure of our agribusiness which relies on very rapid movement of animals and animal products that supplies nationwide - it's a highly profitable and efficient system which was built on the assumption that dangerous foreign animal diseases don't occur here so you don't have to think about what would happen if they did.
We saw in Mexico 65 years ago what happens when you have a slow diagnosis so in 1990 it made no sense to us that diagnosis of these select agents in the US could only be conducted on an offshore island off the coast of New York - which is 3000 miles away, for example, from San Diego, California which is where the last foot and mouth outbreak actually occurred.
It was probably a dream come true to a farmer in California in 1956 that at last we had a place in the Americas where you could make such a diagnosis. But in 1990 with California the 14th largest economy in the world as a single entity and the United States leading dairies state, it really makes no sense to say, "If you want to diagnose these diseases you have to take a sample on an aeroplane to Plum Island." The distance between San Diego and Plum Island is the same distance as between London and Baghdad, so you can imagine what it would be if you said to the british, "You know,take these samples to Baghdad. It's the most efficient way of doing this..." It doesn't make any sense at all. Especially when infection is spreading by the hour nationwide.
So when you have an epidemic, times is the critical dimension. Generally the more time you have, the more options, the more likely that one of those options will be favourable.So diminishing the time to confirm diagnosis of a dangerous disease offers great advantages. IN the 1990s we began to see that fast and accurate diagnosis could be performed close to the source of the problem, using automated equipment with data that could be sent over the internet and monitored by experts at a distant site. The most important diagnostic questions twenty years ago were "How do you distinguish animals vaccinated against foot and mouth disease from those that have had the whole virus infection?" (- because some people believe that animals that have recovered from virus infection are still infectious. And this is used as a reason NOT to vaccinate animals in an outbreak.)
Secondly, "How do you identify animals acutely infected with this select agent infections on or close to the infected premises without a bio containment lab?"
The first problem was solved by Juan Lubroth, then a APHIS graduate student with Fred Brown in 1993. He found that animals that had recovered from foot and mouth disease had antibodies to the non structural proteins of the virus whereas animals given modern vaccines didn't have those antibodies. And that's the basis for a commercial Elisa test that's been marketed internationally for many years now.
The second problem was solved by interagency effort using the IDAHO technology, the portable real-time PCR machine linked by wireless to the internet to perform a real-time PCR diagnosis on the farm or close to the site of the problem.
So by 2000, the real time PCR tests were available on this device for 7 or 8 of these foreign diseases including foot and mouth disease, rinderpest, Classical Swine Fever and others.
In November 2010 there was a meeting here in Washington about the state of the art of select agent animal disease diagnostics that might be used by USDA in the event of a select agent outbreak. And the conclusion of that meeting was APHIS and therefore American agriculture "does not have a validated test" to tell the difference between animals vaccinated against foot and mouth disease and those recovered from infection.
Real time PCR tests have been deployed to the national veterinary lab network for four diseases: foot and mouth, Classical Swine Fever, Avian influenza and Newcastle Disease. These are not confirmatory tests. The sample will still have to go to Plum Island. Real time PCR tests for two other diseases are still in validation.
There are no validated laboratory network real time PCR tests or other deployed diagnostics for the other 21 foreign select agents, and APHIS does not have technologies for diagnostics of individual animals, herds or animal products.
Now we are talking here about real time PCR and PCR in general - a technology that has been around for twenty odd years. It's not as if these tests don't exist. They have been invented by lots of labs around the world and validated and used by lots of countries.
What we're talking about is a situation where they're just not available to protect our agricultural economy. Even in 2011, ten years after we started with this.
This is really a massive and sustained failure to transfer scientific discovery to practise and protect national security.
And this failure is compounded by rapid advances in more complex diagnostic techniques that allow you to search for hundreds of agents at the same time in the same sample.
So if we can't provide our first defenders with real time PCR for more than 4 of the 27 priority diseases after ten years, how on earth are we going to get them the enhanced diagnostic tools that can look at hundreds of threats at the same time not just 27?
I actually have here an example of a device. I have no financial interest in this. It is a portable real time PCR machine . You're just going to get a quick course in how you actually do PCR because it requires no intellectual capability - which is why I can do it.
Here is a sample tube. You twiddle your swab in here and put the sample in it. You attach it to this tube here. All the reagents are self contained inside. You press the button, close the lid - and 45 minutes later it gives you an answer. 60 minutes later if it's reverse transcriptase. That's it. That's the technology, that's the skill level you need - and you put the test you want into that.
George has done a wonderful description of the future and the threats we might face downstream, but since the early 1990s we've had the ability to engineer new strains of foot and mouth disease that don't exist in Nature for which there are no vaccines. Foot and mouth disease is a picorna virus, like polio, which can be synthesised de nouveau. There are 7 different serotypes for which vaccines don't cross protect, more than 70 different types out there in Nature.
If we are not geared up to protect ourselves against these threats that have been around a hundred and odd years, it's actually just an academic exercise to worry about other strains that might evolve in the future.
So, I'll conclude by saying that this session is actually on life science trends that are worth watching. The trend I've outlined today is worth watching but it's unfortunately a very negative one.
It's not that the science and technology for vaccines and diagnostics isn't there. New platforms are evolving by the day. But for 25 years there has been a sustained failure to reduce this science and technology to real tools that have been tested in the real world and actually made available to protect the US economy.
The President's tremendous goals, which have been expressed clearly for the first time, are being let down by this, and this is a trend that just has to stop."
(Ends - but see at the top of the page what Dr Breeeze added at the end of the question session.)