00:00:00 Can you tell me about the beauty of viruses?
00:00:04 Viruses are definitely facinating.
00:00:07 If you go out into nature you'll see plants, animals, bacteria, fungi...
00:00:14 What you don't see is that they all carry viruses, not just one but multiple viruses.
00:00:22 So the biodiversity of viruses is much higher than the biodiversity of things you can see with your bare eyes.
00:00:28 These viruses all look different, they belong to large families.
00:00:34 But if you look at them with an electron microscope you'll see
00:00:38 beautiful symmetrical structures, little bars or sometimes ugly polymorfic creatures.
00:00:48 What is special about these virusses is that most of their hosts don't become ill, don't die.
00:00:55 The viruses are completely innocent.
00:00:58 However there are a limited number of viruses that can do significant damage to their host.
00:01:07 It's special that such a tiny creature, in a large organism like an elephant, can cause so much damage.
00:01:18 Are they living creatures? Is it life?
00:01:22 Viruses have genetic material, in that sense they are the same as bacteria,
00:01:29 fungi, plants or animals, but formally they are not alive
00:01:33 because they don't have their own metabolic system.
00:01:36 They are completely dependent on a host for multiplying their genetic material.
00:01:42 So they are not alive, but based on their genetic material they are oganisms.
00:01:48 Why are you so facinated by viruses?
00:01:51 Viruses are incredibly diverse, in nature you can see plants, animals and fungi
00:02:00 which look beautiful, very diverse, but you might not realize
00:02:04 all those organisms carry viruses, multiple viruses for every host.
00:02:10 So the biodiversity of viruses is much larger than you can see with you bare eyes.
00:02:17 Most of those viruses don't cause any trouble for their host,
00:02:24 it's a very limited number of viruses that cause illness or death in their host.
00:02:33 But it's admirable that such a tiny invisible organism is capable of killing, say, an elepant.
00:02:45 Could you say the earth is more or less populated by viruses?
00:02:51 Yes, viruses are so diverse you could state the earth actually belongs to them.
00:02:58 Some theories of evolution say all life on earth comes from tiny bits of multiplying genetic material,
00:03:11 which in fact is a virus. So viruses are the foundation for all life on earth.
00:03:17 That is one of the prevalent theories within evolutionary theory.
00:03:22 And there are clear indications for this.
00:03:25 A large part of human genetic material consists of elements that once used to be viruses.
00:03:33 Those viruses played an important role in the evolution of humans,
00:03:37 the fact that women have a placenta is because of former virusses.
00:03:47 So the placenta only came into existence
00:03:50 because of a virus that entered the genetic material of an organism.
00:03:56 Thus viruses are a vital part of the evolution of everything on earth.
00:04:04 You could say viruses conquered the world.
00:04:09 That's comlicated, something of a chicken and egg situation.
00:04:14 First there were viruses, then something bigger evolved.
00:04:18 So in fact humans conquered the world using those viruses.
00:04:25 I think that's a more correct understanding of what happened.
00:04:29 We defeated viruses and conquered the world.
00:04:32 We are alive thanks to the existence of viruses
00:04:36 thanks to viruses we are what we are,
00:04:39 plants and animals are what they are.
00:04:42 But we can now handle viruses
00:04:48 combat them with medication, vaccines and preventive measures.
00:04:53 So we are conquering the viruses, yes.
00:04:58 What was your personal motive to start working on viruses?
00:05:03 I graduated in 1984, when it was discovered HIV was the cause of AIDS.
00:05:11 And I was handed a job I simply couldn't refuse.
00:05:17 Up until that moment we thought we had beaten the world of viruses,
00:05:24 we eliminated smallpox, we were busy eliminating measles,
00:05:30 we actually thought viruses would dissapear. But then there was AIDS
00:05:34 and after that hepatitis and other substantial viral infections.
00:05:39 So I got the chance to work on AIDS,
00:05:42 which I did with great joy for the first 10 years of my career.
00:05:45 But after those 10 years, after lots of basic research,
00:05:50 people with AIDS could live,
00:05:54 we can't completely cure it yet, but we can prevent an early death from AIDS.
00:06:01 That gave me the feeling that my work,
00:06:04 the basic virology reasearch on AIDS, was done
00:06:08 and I should start doing something else,
00:06:09 so I started working on a respiratory virus.
00:06:12 Why do you think you lab is considered to be one of the best in the world?
00:06:20 That's by virtue of the vision of the professors that used to run the lab
00:06:27 it's been a virology department for a long time.
00:06:31 At first run by professor Mulder, Masurel and Osterhaus
00:06:34 and they brought together a very diverse team, it's multidisciplinary,
00:06:42 has ecologists, pathologists, immunologists, virologists, all working together.
00:06:53 They are all relatively young and very enthusiastic people
00:06:58 together they can analyse any problem,
00:07:03 they have all the tools that are needed to do virology research.
00:07:08 That's owing to 50 years of virology lab in Rotterdam.
00:07:13 You have a large archive and a new laboratory
00:07:17 We have an extensive collection of viruses, from humans and animals, dating back to 1930.
00:07:27 We have a great number of freezers filled with samples of viruses.
00:07:35 And we use those for lots of research.
00:07:37 There are wild animals, birds, bats and zoo animals,
00:07:43 we once studied the serengeti lion, those kind of things.
00:07:48 Additionally we have facilities that allow us to work with pathogenic viruses
00:07:56 you can't just bring out to work with.
00:08:00 We built special labs, so called BSL3 labs, biosafety level three,
00:08:06 where you can safely work with the viruses, without the risc of infection
00:08:12 and without the risc of villains stealing a virus.
00:08:18 The laboratories are protected in two ways.
00:08:21 And there we can research the viruses using both cell and tissue culture systems
00:08:27 and test animals.
00:08:30 You want to keep the viruses in and malevolent people out.
00:08:34 Yes, in our labs we have two forms of safety: biosafety and biosecurity.
00:08:43 Biosafety means keeping dangerous viruses away from people.
00:08:50 Biosecurity means keeping dangerous people away from viruses, to prevent abuse.
00:08:58 You work on respiratory viruses, what kind of research do you do exactly?
00:09:06 Our research covers everything from the very beginning of the viruses to the end.
00:09:14 My research is about the evolution of these viruses, so we start with their natural hosts, birds
00:09:24 we do field studies and try to understand the evolution and spread of these viruses in birds.
00:09:31 Some of the viruses can spread to poultry, we try to understand why some can and others can not.
00:09:41 If we know the answer we might be able to prevent outbreaks.
00:09:47 In poultry the H5 en H7 influenza viruses can evolve into highly pathogenic forms
00:09:54 that cause death chickens within 24 hours.
00:09:58 We have no idea how it works. Why is it just these two viruses and why is it just in chickens?
00:10:06 We try to understand the evolution so we can do something with that knowledge.
00:10:11 Once poultry has been infected, it can be transmitted to pigs.
00:10:18 When livestock is infected, it can spread to humans.
00:10:24 You can see evolution processes, how a virus adapts to it's new host, a human.
00:10:31 We try to understand that proces.
00:10:37 The final step, when a virus can be transmitted between humans, it becomes endemic,
00:10:49 we try to understand how it has evolved to escape our immune system
00:10:55 and the flu shot sometimes doesn't work.
00:10:57 We try to understand all facets of the evolution of viruses, from birds to humans,
00:11:06 so we can intervene and prevent outbreaks in poultry, prevent human pandemics
00:11:14 and to improve the flu shot.
00:11:17 Studying this evolution allows us to develop completely new intervention strategies.
00:11:26 Influenza viruses can cause a lot of trouble...
00:11:30 Yes, influenza has two forms of activity in humans, epedemics and pandemics.
00:11:37 Pandemics, woldwide outbreaks of a virus new to humans, can be very severe.
00:11:46 In 1918 a pandemic caused 15 million deaths, the last pandemic in 2009 was less severe.
00:11:54 In the future we want te prevent those pandemics.
00:11:58 For the last two centuries they happend every 20 to 30 years.
00:12:07 And we are trying to prevent these pandemics from happening,
00:12:11 we don't know if the next one will be mild,
00:12:14 or severe like the one in 1918 when millions of people died.
00:12:21 We know pandemic viruses jump from animals to humans.
00:12:27 In humans they develop the capacity to spread through the respiratory system,
00:12:34 by coughing, sneezing and breathing.
00:12:37 That is what distinguishes a pandemic virus from all other viruses.
00:12:44 My research group tries to understand is how a virus becomes contagious through the respiratory system.
00:12:52 On the one hand it's purely for fundamental knowledge, we don't know what makes a virus contagious.
00:13:03 On the other hand, if we know how it works, we will be able to do something about it.
00:13:11 We can develop new intervention strategies to stop a pandemic and save many lives.
00:13:19 That is the goal of my research.
00:13:22 The research caused you quite some trouble in 2011, can you tell me what happened?
00:13:30 In 2007 we started to research the contagiousness of animal viruses in humans.
00:13:43 In 1997 we saw bird flu viruses that could infect and kill humans for the first time
00:13:52 very virulent forms of avian influenza.
00:13:55 Sinds 1997 everyone has been wondering if such a virus will cause the next pandemic,
00:14:05 one that might be like the spanish flu pandemic.
00:14:10 So we need to find out if the H5N1 virus really can be transmitted between mammals through the respiratory system.
00:14:19 We can't research this in humans, so we do animal testing, we use ferrets.
00:14:29 We mutated a H5N1 virus, using all our knowledge on pandemics
00:14:42 then we put the virus in the resperatory system of a ferret and let it adapt.
00:14:56 That way you can test if the virus can be transmitted to other ferrets by sneezing, coughing or breathing.
00:15:07 In 2011 we proved the Asian H5N1 virus can in fact become airborne.
00:15:20 That was new, we were the first to discover it.
00:15:23 So we need to be cautious around the H5N1 virus, warn the world health organisation and the involved countries in Asia.
00:15:36 But we also gained fundamental knowledge on how a virus becomes airborne.
00:15:42 This information can be used in surveillance studies
00:15:46 to see if such viruses are already emerging in the field, in that case we can start culling.
00:15:55 Above all this is the fundamental knowledge we had been waiting for in the field of virology.
00:16:03 We don't understand how a virus becomes contagious, yet here, we have two viruses,
00:16:10 an original H5N1 virus and one that is airborne. Now we can find out how a virus becomes airborne.
00:16:18 That is precious scientific knowledge.
00:16:22 Unfortunately the American gouvernment was afraid terrorists would use this knowledge
00:16:32 to make other viruses airborne, use it as a bio-weapon.
00:16:38 Due to the fear of the American gouvernment the publication of our research was initially forbidden.
00:16:48 Of course we took action, the information could possibly be abused
00:16:57 but more importantly it could definitely aid science and public health.
00:17:05 By culling and preventing pandemics we can save more lives than by hiding the results.
00:17:16 After months of discussion on whether this kind of information should be published
00:17:21 the American gouvernment, the World Health Organisation and the Dutch gouvernment decided it should be.
00:17:30 It advances science and public health.
00:17:34 But you were threatened, people blamed you for doing this.
00:17:41 In october 2011 the American gouvernment told us the research could not be published.
00:17:54 And we were not allowed to communicate about it.
00:17:56 The Dutch gouvernment took their advice,
00:17:59 as a result the popular press got the idea that we did something terrible,
00:18:07 they reported that Fouchier's lab created a bio-weapon that could destroy the world.
00:18:17 The New York times wrote an absurd editorial calling it 'the doomsday virus'.
00:18:24 They did this because they didn't know the facts.
00:18:29 Withholding the manuscripts, not sharing our actual findings, caused commotion.
00:18:40 Simply because of the lack of knowledge. We were not allowed to explain the situation.
00:18:49 All this lead to a smear campaign against my research group and against me personally.
00:19:00 You were really threatend personally, right?
00:19:01 Yes, very quickly there were threats on the internet
00:19:05 about what kind of car I drive, push him off the road, where my children go to school.
00:19:11 It went that far?
00:19:13 Yes, unfortunately. I had police officers at my office, driving through my street. A shame.
00:19:22 Do you ever look back?
00:19:24 These things really affect you as a scientist.
00:19:29 Usually we are completely transparent in everything we do.
00:19:36 We work with students and foreign guests, we freely communicate
00:19:40 and enjoy academic freedom, freedom of the press, we are payed with tax money.
00:19:47 So we prefer to be open to the whole world.
00:19:51 Now, however, it seemed like I used tax money for bio-weapons, against public health,
00:20:04 instead of for public health, like I thought I was doing.
00:20:08 That switch in the notion of what kind of work we do, really affects you.
00:20:17 It turned into Dr. Strangelove.
00:20:19 Dr. Strangelove was mentioned, those sketches were on internet, I was depicted that way.
00:20:30 It was taken very far...
00:20:31 Yes, unfortunately at that moment due to a lacking exchange of information.
00:20:41 It shows how important freedom of expression is for the press and science.
00:20:48 This freedom is extremely important.
00:20:50 We can only defend ourselves by explaining what we did,
00:20:55 why we did it and how did this safely.
00:20:58 Do you ever feel like you have to watch your back, fear for your safety?
00:21:03 Even when we were threatend on the internet I never really felt unsafe.
00:21:10 I always viewed them as quite harmless idiots
00:21:19 though the police did feel they had to warn me, so it was someting.
00:21:26 I wasn't too worried about myself, I was more careful about my wife and kids.
00:21:36 I think I was a bit more free than my children at that moment.
00:21:41 It shows how great the fear of viruses is.
00:21:46 Viruses have a bad reputation, they make you ill, you can't see them
00:21:56 so they are scary.
00:21:58 But people don't realize viruses are everywhere.
00:22:01 If you go swimming in the ocean, you're swimming in a pool of viruses.
00:22:05 If you go swimming in a lake, it's also filled with viruses.
00:22:08 But nothing happens.
00:22:09 Most viruses are harmeless, at utmost only infective in one host.
00:22:18 A virus in a chickens is usually harmeless to humans.
00:22:22 But there are many movies where people turn into zombies because of a virus
00:22:29 or a virus kills 99% of the population, exept for one hero, who finds a vacciniation.
00:22:39 That is what people know, but it has nothing to do with reality, with real viruses.
00:22:52 But you are occupied with beating viruses, disarming them?
00:23:00 Laboratories like mine do two things, we try to beat viral infections
00:23:10 using medication and vaccinations.
00:23:14 We also research viruses for practical use.
00:23:21 For example to cure people or to advance our knowledge in biology.
00:23:29 And that's relevant, you are able to predict the evolution of a virus.
00:23:37 All the research on the evolution of influenza viruses
00:23:42 from wild birds to human epidemics
00:23:46 are aimed at predicting that evolution.
00:23:49 Sometimes people find that funny, you can't predict evolution
00:23:54 and indeed it is nearly impossible
00:23:57 if, for example, you want to predict what people will look like in ten thousand years.
00:24:00 But for viruses it is much easier.
00:24:03 Viruses have a very small amount of genetic material
00:24:08 an influenza virus' gentic material has fifteen thousand buiding blocks
00:24:14 those fiteen thousand you can still count and read.
00:24:16 Furthermore we know what drives the evolution of these viruses.
00:24:23 Once a virus jumps from animal to animal, or to humans
00:24:28 we know what has to change in the virus to adapt to it's new host.
00:24:34 The most important driving force for a virus in a human, is our immune system.
00:24:43 The virus needs to escape our immune system.
00:24:46 The system of a virus in it's host is so simple, we can perfectly understand it.
00:24:55 If we understand this and how it relates to the genetic material
00:25:01 we can easily predict the evolution.
00:25:04 Once we can predict the evolution, we can be ahead of it.
00:25:08 We can make better vaccines and beter medication,
00:25:11 better preventive measures, that is the goal of my research.
00:25:15 You say it is simple, it can't really be?
00:25:20 It is much simpler than the evolution of a plant, human or animal.
00:25:27 A flu virus had a small number of genetic building blocks.
00:25:30 So little I can count them, read them and understand what they are saying.
00:25:37 And the driving forces of their evolution are really simple.
00:25:39 Because we only have to watch a limited number of factors
00:25:45 we can start to understand the evolution and eventually predict it.
00:25:49 But it's not something that happens over a period of one or two years.
00:25:54 I have been occupied with influenza viruses for 15 years
00:25:58 and now I have started to test the first predictions in clnical studies.
00:26:04 The predictions are on how the virus evolves in humans
00:26:08 and escapes our immune system, so we continually have to updat the flu shot.
00:26:15 We predict what a virus will look like in two years
00:26:22 we already create a vaccine, to test if it might work better that the one we have.
00:26:30 We predict the virus and intervene to see if we can prevent it.
00:26:37 You even developed computer programs to calculate these things.
00:26:42 In 1998 we started to develop programs to map the genetic material
00:26:52 and the biological attributes of a virus.
00:26:56 So we can see how the genes and biological attiributes evolve over time.
00:27:06 And now we can recognize very distinct paterns.
00:27:09 These paterns are so clear we can predict what will happen next.
00:27:17 If you see evolution along a straight line
00:27:20 it's not very hard to predict where the virus will be in two years.
00:27:24 It'll be at a surtain point along that straight line.
00:27:28 That is what we find in the antigenic drift of a virus,
00:27:33 the way they escape our immunse system.
00:27:36 We think this antigenic drift is so predictable
00:27:41 we can develop a flu shot now, that we'll use in two years.
00:27:46 What does that promise for the future?
00:27:50 Virus research has always been the base for lots of other research
00:27:59 because viruses are simple.
00:28:00 So viruses are the starting point for research
00:28:03 and afterwards you can translate the results to other organisms.
00:28:08 Bacteria, fungi, plants and animals.
00:28:12 Eventually if we really can predict the evolution of a virus
00:28:19 I don't see why we wouldn't be able
00:28:22 to predict the evolution of a plant or an animal in a hundred years.
00:28:26 That is a trend we've see in the past
00:28:30 first discoveries are done on bacteria and viruses
00:28:34 because they are small and easy to understand.
00:28:37 But in higher organisms the processes are exaclty the same.
00:28:43 So if we show we can predict something simple like the evolution of a virus
00:28:49 we can undoubtly eventually do the same for properties of higher organisms.
00:28:55 What would that mean?
00:28:56 It could mean we'll be able to predict new crops, new species.
00:29:07 How they'll develop as a result of changes in our ecosystem.
00:29:13 Form Darwin's theory of evolution we know
00:29:19 the environment determines how an organism evolves.
00:29:23 By shaping the environment you can shape the organisms living in it.
00:29:34 This is thinking outside the box, many people believe you can't predict evolution.
00:29:42 But I think we'll show you can, beginning with simple processes,
00:29:48 but eventually you can use the same approach on higher organisms
00:29:54 and maybe adapt the environment to stear evolution.
00:29:58 Perhaps we want to know what humans will look like in ten thousand years.
00:30:03 What you are saying is, with the knowledge of viruses
00:30:07 we don't just conquer the viruses, but genetic endowment.
00:30:12 Because of these viruses we'll really gain a better understanding of evolution.
00:30:17 Evolution theory is complex, but by using a simple virus you can understand it.
00:30:28 And the evolution of a virus is fundamentally not different from a plant, human or animal.
00:30:35 So by really understaning viruses, I think we'll indeed be able to translate it
00:30:44 to higher organisms and guide and predict evolution.
00:30:48 That's one thing, another is you can use viruses as a tool.
00:30:55 Viruses are simple, they don't have many genetic building blocks
00:31:02 especially the viruses I work on, RNA viruses.
00:31:05 We completely understand their building blocks.
00:31:08 We know which ones we can remove, how to change them
00:31:13 so we change the properties of a virus.
00:31:17 That's why a virus that would kill us 30 years ago, AIDS/HIV,
00:31:26 can now be used to cure children with an autoimmune disease.
00:31:35 We understand how the HIV virus multiplies,
00:31:42 we remove pieces from the genetic material, so it is no longer pathogenic.
00:31:49 It can't autonomously multiply anymore
00:31:52 and the pieces we removed can be replaced by a gene of our choosing.
00:31:57 We can choose a gene that had a defect within the patient population.
00:32:04 That way HIV based gene therapies are developed.
00:32:12 The HIV that used to make you ill is changed
00:32:16 using the copy of a correct gene that is faulty within the patient population,
00:32:22 next you infect the children with the HIV virus to heal them.
00:32:30 40 years ago we never would've predicted
00:32:33 we would understand a deadly virus like AIDS so well
00:32:37 that we'd be able to change it a bit and use it to cure children.
00:32:45 In stead of just fighting viruses you can also use them now?
00:32:51 We use viruses to repair fautly genes in patients.
00:33:00 A fault gene, an immune defect, can cause patients to die very young.
00:33:10 And now we tweeked HIV, a virus that caused AIDS and death 30 years ago,
00:33:19 in such a way it can now cure these young children.
00:33:25 We completely understand the AIDS virus, know all the genetic building blocks.
00:33:29 We can remove the blocks that would normally make people ill
00:33:34 and we can replace them by a gene of our choosing.
00:33:37 In this case a the correct gene which the children are missing.
00:33:42 We use the virus as a method to provide the genetic material that was missing.
00:33:55 The virus enters their cells
00:33:59 and they grow into healty cells with the correct copy of the gene.
00:34:05 So viruses that were deadly 30 years ago are now used to cure children.
00:34:12 What does that mean for the future?
00:34:16 We say our research is important for fundamental science
00:34:27 but of course there practical applications.
00:34:30 If I understand how an influenza virus is transmitted through the respiratory system
00:34:35 how it is stable in an aerosol
00:34:39 and which cells in the respitory system it can infect
00:34:44 you can immagine I'll be able to replicate the virus
00:34:47 add proteines and make a nano particle
00:34:56 that has the same properties as the influenza virus
00:34:59 but is is filled with medication.
00:35:02 I'd be able to give mediation to all the cells in my repiratory system through a spray.
00:35:09 With particles that look like the influenza virus,
00:35:11 they are airborne and stable
00:35:16 and target the cells of the epithelium.
00:35:19 It might be a way to treat patients with cystic fibrosis.
00:35:23 It's all wishful thinking, but that's how science works.
00:35:29 We do basic research to understand fundamental problems
00:35:36 and we don't know which one have practical implications yet.
00:35:42 We can think about it, but we won't know for sure.
00:35:48 It's special, on the one hand you combat them, on the other hand you use them.
00:35:52 Whether you combat or use a virus, the research method is the same.
00:36:03 You need to know exactly how a virus works.
00:36:06 How it enters a cell, why it destroys the cell and how a virus spreads.
00:36:13 If I know how a virus spreads, I might be able to stop it.
00:36:17 If I know how it destroys a cell, I might be able to stop it with medication.
00:36:22 If I know how our immune system reacts to a virus,
00:36:25 I can prepare it with a vaccine.
00:36:28 Research for combatting viruses and using viruses is identical.
00:36:40 You need to understand every detail of how a virus works.
00:36:43 Are you informed of potential epedemics and pandemics?
00:36:54 The past 15 years we developed tools to map epedemics.
00:37:04 The evolution of the genetic and biological properties of a virus
00:37:09 can be quantitatively tracked by a mathematical tool.
00:37:18 These tools are a mathematical methods using lab data.
00:37:25 The world health organisation now uses it to map all viruses.
00:37:32 So we have real time acces to data on how all viruses in the world evolve over time.
00:37:40 That is an great source of information, not just for improving and updating the flu shot
00:37:47 but also for research on the evolution of viruses.
00:37:52 If everyone in the world isolates and analyses ten thousand viruses every year
00:37:59 and sends us data for analysing, we get amazing data sets.
00:38:07 And in case of a code red, what happens?
00:38:10 A code red is when new viruses are transmissable from animals to humans.
00:38:20 Laboratories like ours, with a broad selection of specialisms,
00:38:28 are asked to assist research.
00:38:31 We did this in 2003 during the SARS outbreak, in 1997 with H5N1,
00:38:39 in 2012 with the outbreak of MERS, at the moment with ZIKA.
00:38:46 We are asked to help with research.
00:38:51 It starts with very basic questions. Why is this virus transmitted to humans?
00:38:57 Why do we becom ill? Why do we die?
00:39:00 Is there something we can do, can we develop a vaccine or medication?
00:39:04 These are very practical questions our department had been able to answer.
00:39:10 So they call us when there is an outbreak, it's a great honour
00:39:15 and we like being able to contribute to public healthcare.
00:39:21 But this also provides us with material for further research.
00:39:26 We can answer those basic questions quite quickly
00:39:29 but finding out how a virus really works takes many years of research.
00:39:37 And we can do that research because we were involved from the beginning.
00:39:46 Can you immagine there being a universal vaccination for the flu?
00:39:51 The holy grail within the world of viruses is a universal flu shot.
00:40:01 At the moment we create a flu shot for the current influenza virus.
00:40:08 We take a look at the epidemics every year
00:40:11 to see which viruses are ciruclating, and we make a vaccine.
00:40:16 But there is a huge diversity in influenza viruses, in all kinds of animals.
00:40:24 A vaccine that protects against all these forms would be ideal.
00:40:30 Our lab researches this, together with many others,
00:40:34 including the farmaceutical industry.
00:40:36 That's why it's the holy grail.
00:40:39 If you can develop a vaccine against all influenza viruses
00:40:43 you are, what we would call, in business.
00:40:47 I do think such a vaccine will be developed.
00:40:50 It might take 10 or 15 years of research, but I am convinced we'll get there.
00:40:57 We'll completely conquer viruses?
00:41:00 We'll definitely conquer influenza viruses.
00:41:03 I expect I'll have to look for a different job in 15 years
00:41:08 because the flu, just like AIDS, won't be deadly anymore.
00:41:17 You're lab was feared... Are there still things you have to keep secret?
00:41:29 My lab does not have any secrets.
00:41:32 My research is funded by tax money, I work with students a lot.
00:41:38 Master students and PhD students,
00:41:41 post docs from all over the world.
00:41:44 In a completely transparent way, we don't try to keep anything to ourselves.
00:41:49 There is research done in so called classified labs
00:41:54 belonging to the American, Chinese or Russian army.
00:41:59 They research the threat of bio-warfare.
00:42:04 But it's not what we do, we do research to aid public health and animal welfare.
00:42:12 Let that be clear. We saw the ducks...
00:42:19 Can you tell me why you have them?
00:42:25 Wild birds are the natural reservoir for influenza viruses.
00:42:30 All viruses we know in humans come from animals.
00:42:36 Wild animals are natural reservoirs for those viruses.
00:42:41 Bats are a notorious reservoir for cronaviruses like SARS and MERS.
00:42:48 And wild birds are the reservoir for all influenza viruses.
00:42:52 All influenza viruses we know, avian influenza in poultry
00:42:55 swine influenza, the flu in humans... All come from wild birds.
00:42:59 To understand and handle the virus in pigs, humans and poultry
00:43:05 you need to understand what happens in that reservoir.
00:43:08 In the natural reservoir like wild ducks, sea gulls.
00:43:14 You need to understand how the virus evolves in those hosts, in wild birds.
00:43:20 Know the genetic and biological diversity.
00:43:26 Some viruses can be transmitted to poultry or pigs, but others can't.
00:43:34 You have to start you research with those wild birds.
00:43:39 There's just one way to do that, you have to catch a lot of wild birds.
00:43:43 An infected bird only sheds the virus for 5 days
00:43:49 so you have to catch a great number of birds to map all viruses.
00:43:55 We've been doing this for 15 years, in the Netherlands and other countries.
00:43:59 Slowly we are starting to understand
00:44:01 how these viruses drift around the world in wild birds
00:44:08 and how they end up in poultry, pigs and humans.
00:44:13 So you take them and analyse them in here?
00:44:15 We've set up a network of ornithologists all over the world.
00:44:26 They send samples form the cloaka or throat of birds to my lab.
00:44:40 And we test it for influenza viruses.
00:44:43 In that case we isolate it in our lab.
00:44:48 After we've cultivated it, we can genetically characterize it,
00:44:54 we can map all the genetic material.
00:44:59 And we can determine the biological properties,
00:45:03 we can find out if the virus can infect the cells of mammals,
00:45:09 if it can escape our immune system, things like that.
00:45:15 So these viruses are characterized elaborately.
00:45:20 How difficult is it to change a virus?
00:45:29 For some virus families it is very easy, for others very difficult.
00:45:41 There are small viruses, large viruses, RNA viruses, DNA viruses...
00:45:45 I work on respiratory viruses with an RNA genome, they aren't too large,
00:45:52 and you need special expression systems to make them.
00:46:01 It isn't simple, but is has become a routine job.
00:46:06 Once you have a well trained team of molecular biologists
00:46:10 you can easily make a couple of new viruses every day.
00:46:14 But for a new team it would take 6 or 7 years to get the hang of it.
00:46:26 It demands a high degree of specilization.
00:46:31 It's doable for your team?
00:46:32 Yes, we make viruses on a daily basis.
00:46:36 We make viruses with up to 3 point mutations in the genes.
00:46:41 Sometimes we add genes to a virus, fluorescent proteines for example
00:46:47 so you get a fluorescent virus
00:46:49 and you can easily see how it infects a test animal.
00:46:58 Sometimes we remove a gene to see how we can disable it
00:47:07 and possibly turn it into a vaccine.
00:47:11 It's facinating, they're so tiny you can hardly see them with a regular microscope
00:47:19 however you can change them, change the genetic material.
00:47:26 You can clone a viruses' genetic material,
00:47:32 grow it in bacteria, so you get tons of it.
00:47:39 Then you can cut and paste.
00:47:41 Simply put, you can cut and paste pieces of DNA and RNA.
00:47:49 You can make any combination you like.
00:47:52 However most combinations won't work.
00:47:57 But if you understand a virus
00:47:59 you'll know how to cut and past in order to change the virus.
00:48:07 After you've mutated the genetic material
00:48:13 you can extract the DNA from the bacteria
00:48:16 and transfer it to a mammal cell in a culture dish.
00:48:21 If you do it using the right DNA you can create a virus.
00:48:27 It sounds simple, and it is if you know what you're doing,
00:48:32 but a nonprofessional won't be able to do it.
00:48:38 Viruses are like machines, geometrical, with a special structure.
00:48:46 Viruses are in fact tiny nano machines
00:48:52 pieces of genetic material, packed in proteines, to protect it.
00:48:59 Some proteines, polymerases, make sure the genetic material will multiply in a cell.
00:49:10 The genetic material is protected from outside air in a wax ball
00:49:16 which has thornes to help it attacht to a cell.
00:49:26 It's a nano machine, a wax ball, with genetic material
00:49:30 and proteines that help it to infect a cell, multiply and infect the next host.
00:49:38 We can use those characteristics for our benefit.
00:49:44 You can use a virus to put genetic material into a cell.
00:49:51 Depending on the kind of virus, a respiratory virus,
00:49:57 a liver virus, or a virus carried in the blood,
00:50:00 based on those characteristics you can build a new nano machine
00:50:08 that targets genetic material in the cells of the lungs, blood or the liver.
00:50:17 That's what we now use viruses for.
00:50:20 That is really happening?
00:50:21 Yes, we can put genes in the blood of people with an immune disease
00:50:29 so their genes can be repaired.
00:50:32 We can make viruses so they destroy tumor cells instead of normal cells.
00:50:42 We can use viruses to treat cancer.
00:50:47 Those are all applications of viruses that are already being used.
00:50:51 The first drugs to repair gene defects and cure cancer are on the market.
00:50:57 Where will that take us?
00:50:59 I think eventually virology will really contribute to public health.
00:51:05 We'll solve many gene defects and forms of cancers,
00:51:10 by using genetically modifying viruses to cure people and animals.
00:51:19 Is that a promise? Or is it an uncertain probability?
00:51:29 We can already cure a number of illnesses using viruses.
00:51:35 We can repair a gene defect using the AIDS virus.
00:51:45 We can cure skin cancer using a genetically modified herpes virus.
00:51:55 We're working on other viruses that can infect tumors cells
00:52:07 and start a massive immune reaction
00:52:11 so the immune system will clean up the tumor.
00:52:15 It's called oncolytic immunotherapy
00:52:18 using a virus that kills tumor cells
00:52:22 and also starts a immune reaction against them.
00:52:30 So your own body will clean up the tumor.
00:52:32 It works really well in mice,
00:52:35 in our lab we've done it on mice with pancreatic cancer,
00:52:42 and using a modified virus it completely dissapeared.
00:52:48 We'll need to do more research before we can do it for humans.
00:52:54 But we're working on it very hard.
00:52:56 And I am convinced, in 10 years, we'll be able to cure many forms of cancer
00:53:03 using immunotherapy or viral immunotherapy.
00:53:08 Viruses as a universal medicine.
00:53:12 Viruses as an engineered nano particle
00:53:18 which you specifically target
00:53:21 so you use the viruses' beautiful properties to benefit it's host.