Horizons Talks: High Impact Pandemics: From crisis to preparedness
The Horizons Talks speaker series brings experts from Canada and around the world to share their forward-looking research and ideas with public servants.
Are high impact pandemics only a matter of time?
Dr. Rudi Pauwels, founder and president of Praesens Foundation and co-chair of the diagnostics R&D working group that is part of ACT – A Global Collaboration to Accelerate the Development, Production and Equitable Access to New COVID-19 diagnostics, therapeutics and vaccines shares his work on pandemic preparedness and response. He discusses the need to build resilient and sustainable systems to monitor, detect and respond to infectious disease threats.
Covid-19 is a reminder of the impact that outbreaks and pandemics can have on peoples’ lives, their livelihoods, as well as economic growth and development. History shows that such events are just a matter of time. Yet, despite the growing number of outbreaks in recent decades, the world remains vulnerable and needs to shift from crisis response to preparedness.
Video
Speaker
Dr. Rudi Pauwels
Dr. Rudi Pauwels studied pharmaceutical sciences and virology at the University of Leuven (Belgium). He is a serial bio-tech entrepreneur with 35 years of experience in pharmaceuticals and diagnostics. In the mid-eighties he described the first methods to search for anti-HIV agents. His academic work and the efforts of the team he led at Tibotec, resulted in several new anti-HIV drugs that are now widely used to treat HIV-infected patients.
Since a few months, Dr. Pauwels is co-Chair of the diagnostics R&D Working group that is part of ACT – A Global Collaboration to Accelerate the Development, Production and Equitable Access to New COVID-19 diagnostics, therapeutics and vaccines. Read more.
Transcript
KRISTEL VAN DER ELST: Good morning, everyone. We’re happy to have, as Imran was saying, to have Dr. Rudi Pauwels here with us. So we are both Belgians. Rudi, I will start my most important part.
Dr. Rudi Pauwels studied pharmaceutical sciences and virology in Belgium, and he’s a serial biotech entrepreneur for over 35 years with experience in pharmaceuticals and diagnostics.
His early work actually resulted in several new anti-HIV drugs that are now widely used to treat HIV impacted patients.
He has been starting a lot of different start-ups within the biotech, and in 2004, Rudi went on to a sabbatical, I think, because he wanted, given his knowledge about the micro and nanotech, and there, he got fascinated by the increasing need for more rapid and easy to use diagnostics to enable personalized medicine in close proximity of patients. And he founded an organization which was called Biocartis in 2007, and that’s how we met, because for this work and for that innovation, Rudi got his Local Technology Pioneer Award from the World’s Economic Forum.
After leading this company for nearly a decade, he decided to refocus on infectious diseases and diagnostics technology innovation, and he got inspired in 2014 as he was involved in western Africa with the Ebola outbreak.
He created a foundation called Praesens Foundation, and that is developing, providing, and implementing solutions that contribute better epidemic preparedness, early warning, and rapid response for existing and emerging infectious diseases.
Since a few months, Rudi is also the co-chair of the diagnostics R&D working group that is part of ACT, which is a global collaboration to accelerate the development, production, and a quick, equitable access to new Covid-19 diagnostics, therapies, and vaccines. It’s a very long name. It is an organization that is global, that has its links to the WHO and in which Canada also has invested.
Now, for me, Rudi also is one of those people I talk often to about Covid-19, and maybe a little anecdote is that when we met at the end of February, you know, remember before all this really started to be hard, I remember him saying, “Well, in four weeks, it will be very, very different. You’ll see.” And boy, was he right.
I’m very honoured that you are here with us today. I look forward to your talk and I’m sure it will be a fantastic conversation.
So Rudi, the floor is yours.
RUDI PAUWELS: Thank you very much, Kristel, and in light of a little bit of technical difficulty of lost time, I decided to stop my video here, continue talking, and Rachel has been so kind to advance my slides.
So if you, Rachel, could set up the slides? Okay, thank you very much.
So good morning, and thank you very much, Kristel, to invite me to give this Policy Horizons talk.
Like you said, it will be a talk about a subject that, I would say, unfortunately, we’re all confronted with every day now. And therefore, I really appreciate that you all are interested to be even more exposed, at least to the subject.
Now, as you just mentioned, Kristel, for the past 35 years, I’ve been active in the field of infectious diseases, and I found myself — I must admit, by some kind of strong attraction — to work at the frontlines of some major pathogen offences.
And I will use similar military terms a few times here for reasons you’ll hopefully appreciate, as I move along.
So battleground, thus, where as Kristel mentioned, not so long ago, we also needed new therapies, vaccines, and diagnostics. And I chose as a title for this presentation, ” High Impact Pandemics: From crisis to a preparedness.” And as I will try to place the current Covid-19 crisis in the urgently needed broader perspective.
I will address four themes, and Rachel, if you can move to the next slide, I will address four themes and then by some conclusions or recommendations, rather.
The first theme introduces what I would call “the unseen enemies”, invisible for the casual observer without a special microscope, at least, yet the effects of the unseen enemies are at moments, all too visible. And we’re just in such a situation.
Now, I like quotes, and this one from Mark Twain kind of best summarizes what I will discuss in this part. And it is that history doesn’t repeat itself, but it does rhyme.
Now, in this case, I could take it even a step further. History does occasionally really repeat itself in scary details even. I’ll also give some illustrations on that.
But these unseen enemies and what they can cause are not just part of history, they are part of our human natural history, as I will illustrate with a few examples.
And I often wondered why the records of past pandemics that even changed at times the course of human history only got some attention in times like now.
Another thing I read somewhere is that history is mostly written by those who have won. The real tragedy is that pandemics don’t really have any winners and that the survivors have been known and shown not to be particularly keen or reminded of the tragic time they went through.
So in a way, we do suffer from some type of amnesia with respect to hard and how hard and the pathogens and pandemics can strike. Therefore, the current Covid-19 crisis should be seen as yet another major wakeup call of the reality of outbreaks and pandemics, and that they are happening just as a matter of time.
There were earlier reports, warning for the likely coming of the new influenza, Corona virus, or other pandemic, and certain science even early in this pandemic should have been taken more seriously. The irregular and timewise very difficult to predict occurrence of these pandemics, of course, doesn’t help. Neither does the complexity of possible converging factors that will tilt the balance whether or not the initial outbreaks spiral out of control and lead to a pandemic or even a catastrophe.
In the third theme, I will highlight a few key observations and take-aways with respect to our urgent need to shift from this crisis to crisis response and move to a much more prepared mode of operation.
Dealing with outbreaks is sometimes compared to firefighting, but I ask the question, do we really have the properly trained and equipped firefighters? Is it, for instance, not only urgently time to invest in smoke detectors and other things that can extinguish the fire before it creates further havoc? And in this part, I will share some of my own present experience and initiatives, as also Kristel already mentioned.
And finally, among the weapons, tools, to fight any outbreak, I will share a few thoughts with respect to diagnostics, whose importance and value is (inaudible) or at least, not fully appreciated.
Now, a few days ago, I read this statement from Italy’s Deputy Health Minister, Pierpaolo Sileri, and I think it nicely sums it up. He says, “Do we get it or not, that we’re at war? We’re fighting to save Italy.”
And he made this statement as a response to the growing protests of at least part of the population in Italy to resist further lockdown measures. And that, you know, echoes what we’ve seen in other parts of the world.
Now, with some serious competition from wars and poverty, it is not much appreciated that before 1900, about half of all human lives ended prematurely because of an infection, and this graph from a few years ago pictures some of the major killers responsible for that high mortality.
The words pestilence, plague, quarantine (inaudible) languages today as a reminder of the bacterial disease that especially in the 14th century swept across the European continent, wiping out nearly half of the population in a matter of years.
A really big one, as they would say in California, was the highly-contagious smallpox, which the World Health Organization declared to be eradicated in 1980 in a rare historical total victory over the pathogens, with thanks to the vaccine.
Its estimated death toll was over 300 million, and we should remember also that smallpox and some other infections are estimated to have wiped out 90 percent of the American Native population, and that is a dark reminder of what can happen when a completely immunological naïve population is exposed to new pathogens.
Now, with the steady advances in medicines, vaccines, better hygiene, those infectious disease related global mortality numbers would drop in the 20th century to about 25 percent, and in developed countries, even much lower.
Now, a few days ago, we rightfully celebrated the end of World War I, a terrible chapter in human history. But also about 100 years ago, the world witnessed the largest pandemic of the 20th century, a pandemic that became known as the Spanish Flu, and it’s estimated to have taken 50 to 100 million lives.
So what do you call something that killed in just the last century alone more women, men, and children than in all combined wars (inaudible)? I think that’s an enemy, an unseen enemy.
In 1981, closer to my own work and that of my colleagues, a new disease was first recognized, now known as AIDS, and that started to spread around the world. It took three years to find the pathogen that caused it, or HIV, a previously unknown member of a family of so-called retroviruses. And we should remember that it was basic research on other members of this particular family that really helped to make that discovery. It soon became clear that receiving the diagnosis of AIDS was nothing less than receiving a death sentence. Mortality after several years living with the virus is over 95 percent, and this predominately sexually transmitted disease can spread from person to person throughout the years a person’s infected.
The rapid rise of mortalities you see in this graph shown here for the U.S., led the world to declare AIDS a global health crisis. But by the mid-nineties, you can also see in the graph that the rising mortality turned around. It’s interesting to note that in pure essence, it were diagnostics and antivirals that are at the basis of this change. Noteworthy too, is that 40 years later, we still don’t have a vaccine yet.
Now, although average mortality due to infections witness the continued positive trends, the number of outbreaks –mind you, more than 10,000 in the past decade, so it’s been steadily since the eighties — and bacteria and viruses were the most common cause of those diseases, the number of outbreaks caused by human to human transmission, enviro factors such as mosquitoes, also climbed. Known factors for this trend include pressure on our ecosystems, growing international trade, more and more travel, urbanization — half of our world population lives in cities today. But also very important, what these trends have shown, is that beyond the local health impact, there are increasingly major consequences for economy, development, and security.
And I would like to take the opportunity here today to highlight another slow, maybe for most of us, invisible pandemic that is linked to the growing anti-microbial resistance, or AMR due to the inappropriate use — maybe abuse — of antibiotics, with trillions of dollars future healthcare and economic impact. And this was according a major U.K. government sponsored (inaudible) a few years ago.
I won’t talk much more about bio tourism, but we should keep that in mind as well.
It’s not that we have not seen earlier outbreaks due to viruses that transmit by the respiratory valves. All the (inaudible) of major influenza pandemics, also viruses, from the Corona virus family came into scope. Now, you need to know that Corona viruses in all the virology textbooks are often described as causing relatively minor symptoms, a bit like the common cold.
But all that changed in 2002 with the SARS outbreak. The SARS virus outbreak caused real damage, also economically, especially in southeast Asia. And it is not so remembered well how it was stopped, not without heroic efforts of the teams who tried to make an end to the chain of transmission. But remember, mortality for this particular virus was 10 percent, much higher than today for Covid-19.
And in a way of speaking, we got a second warning shout that came with MERS, Middle East Respiratory Syndrome, just eight years ago, 2012. The total numbers in infections were lower, but this particular virus was really detrimental when those who became infected, mortality rate was more than 35 percent.
So this leads me to state — you click maybe one more time, Rachel — this leads me to state that although the Covid-19 was just a matter of time, it seems that based on all these trends, it is just a matter of time for what I would call a high-impact level pandemic, one caused by a virus that combines high intrinsic mortality and submission via the airways, and transmission even by people who do not or not yet display disease symptoms.
It is not realizing fast enough this particular capacity of viruses that may have made (inaudible) on this one, and admittedly, the aerosol transmission that is even thought now to peak one or a few days before the onset of symptoms is what makes taking the infected people here so difficult. It is why the wearing of masks, the distancing, and danger of prolonged stays in close, unventilated areas is so important.
Now, in outbreak speak, we say that an outbreak starts with one case and ends with the one case. Yesterday, officially more than 600,000 new Covid-19 cases were reported. So we are clearly there — not there yet.
Many of you probably follow these numbers regularly, so I will not further dwell on them.
With Covid-19, the world is receiving again, as I said before, a major wakeup call. And I can’t help emphasize enough that we need to draw lessons from it. One such big lesson that is made clear is that the problem in one part of the world can become a global problem in every part of the world, and with viruses like this, very, very rapidly.
Secondly, that outbreaks and pandemics are more than a medical problem. We see major disruptions to national and global economies around the world, the need to close schools and businesses for weeks or longer, restrict social interactions, and so forth.
So despite all these signs in January, most of the western world had to react in crisis mode, which exposed weaknesses in preparedness, and that related to our infrastructure, trained personnel, equipment, access to sufficient and rapid diagnostics, and few to no real direct (inaudible) to antiviral teams. I’m sure many of you are involved with the response in Canada are familiar with the points I am raising here.
Within weeks, scientists were able to sequence and publish the genome of SARS-CoV-2, and that is really a big step forward. But there was too fast disease spread for vaccines to make an impact in the first months of the year.
And we all should rightfully be excited about the prospect of a working vaccine that can be distributed in the coming months throughout the world. That’s hopeful. But the elephant in the room is that observation that current vaccine technologies and all the efforts we put into it, the resources, the expert, still, the fact is that it requires 12 to 18 months to design a vaccine, prove that they are safe, that they work, and that they can reproduce that scale.
And last but not least, as also (inaudible) in the last few days, one has to consider the happy logistics to bring and administer that vaccine to millions if not several billions of people.
So when one looks at some of the more (inaudible) of Covid-19 like this one — it’s the (inaudible) from the World Health Organization, it becomes clear that even if the virus has spread globally, the dynamics and the severity by which pandemics unfold is influenced by the scene and the actors in what I would call a kind of play or drama with possible different outcomes.
As I said earlier, infections belong to the ecosystem of humans, so there’s a kind of steady state of infections across populations around the world.
As an example, possibly this year, the jury is still out, but it is not impossible that as many people will die this year from tuberculosis as from Covid-19. But when an outbreak occurs, whether or not it transitions to a pandemic with dramatic or even catastrophic consequences, that will depend on those actors and the scene in which they operate.
The outcome is, in essence, governed, if not determined by the complex interplay of various actors and settings that at times, converge to form a perfect storm.
So Rachel, if you could move, thanks, I’ll need the next slide.
So most of these organisms — I’m sorry — at the heart of all this, there is a triad at work, and the first member of this triad are the viruses, the bacteria, and the other pathogens. And I don’t want to lecture you about virology, but rest assured, there are many, many, many of them. And there are different microorganisms practically in every life-containing niche of the world.
A subset of these organisms, these microorganisms, viruses, bacteria, and others, can become or are pathogenic to man.
And this is saying that they were there long before us and they will likely survive us too.
So most of these organisms have reached what I would call a kind of balanced state of existence within their natural hosts such as bats, poultry, rats, snakes. And there are multiple mechanisms and even more occasions by which these pathogens jump from one species to another.
Now, when the pathogen is sufficiently capable to replicate in the new host, and even more so, when it has furthermore acquired the capacity to transmit between the new hosts, outbreaks start and evolve.
But that’s what we have also now for Covid-19 seen, not all hosts are identical. You saw that very clearly in the dynamics of the outbreak around the world. I mean, there is age, there is the immune status, underlying health conditions, location of the human population, living conditions, their social status, behaviours, travel patterns, environment, the climate they live in. All of these factors will influence the final outcome and whether or not the outbreak aggravates in severity and moves the pandemic with different consequences.
But we can do more, also in the relatively short term, because this is very important. Some of the factors that I just mentioned will take time. We can, for instance, make sure that our living conditions, that we design our society in such a way that we are more prepared, more resilient to the occurrence of these outbreaks. But we can do more. And this include investments in what I would call tools, weapons, that can prevent outbreaks, or at least limit the consequences once these outbreaks occur. And they are listed here. I won’t go in detail to all of them, but this includes well-trained healthcare workers, making sure they are properly equipped, making sure that our healthcare infrastructure is appropriate. This morning you may have seen the news, but in Italy, practically — in certain parts of Italy, all the hospitals are filled. We now have to fill hotels to put in Covid-19 patients.
Science cannot stress this enough. We do need to do the basic science on these pathogens and their consequences. You can’t manage what you don’t know, so intelligence is very important.
And now I’ve come back on diagnostics. We need antimicrobials, antivirals, and this is possible. A lot of my colleagues and myself have pushed the agenda for years now — I don’t know it’s with a lot of support — to design what I would call panfile (phonetic) antivirals. So these are antiviral agents that work on groups or family of viruses like influenza viruses or Corona viruses. And then there is the vaccines, which I already mentioned.
If you can move to the next slide? Thank you.
Now, I mentioned the enemies, unseen, and there are many of them. But one more thing that makes it even more difficult is that they have the extraordinary capacity to evolve and change, pending the selection pressure that they are submitted to. And why do I want to mention this here in particular, because you need to know that that is important to be very, very carefully monitored, because it could reduce the effectiveness of therapeutics, vaccines and also diagnostics.
And also, as we’ve seen in past pandemics, as we move through multiple waves and millions and millions of people become infected, it is not impossible that viruses acquire new biological properties that improve their viral fitness, make them more infectious, and possibly cause more severe disease. It’s not always the case.
And then the last actor in this drama I want to single out today is time, response time, which can be an enemy on us or a foe. We should remind with respect to time first and foremost that we should always emphasize that the primary objective in an outbreak is to stop the chain of transmission, save lives and livelihoods, even if we don’t have a vaccine or if we don’t have treatments. That has been shown in history over and over again, one of the key objectives in any outbreak.
The second point I want to make is that I would say the fastest response is the local response, because the people that need equipment and resources are already there, and losing — avoiding to lose valuable time by bringing the resources there.
The third one — and that is, I think, also not uncommon in firefighting — hit hard, hit early. It’s like in cancer. It’s the lessons we’ve also learned with HIV treatment where in the beginning, we kind of tried one drug after another. It took about a couple of years to realize that we had to come in hard and early to make a long and lasting impact.
Another important point I want to emphasize here is that use those crises to learn, to prepare, and rehearse the scenarios before the outbreaks occur. Another lesson we’ve clearly seen in Africa is that quick fixes are often not quick enough and tend to be short lived. Study, learn, and improve.
And in therefore, I used military terminology a few times here. Outbreaks and pandemic should be compared to wars. You need timely intelligence, the right tools, infrastructure, plain force. Maybe you should think about infectious disease SWAT teams like Ilsadon (phonetic) in China where I know that in the beginning of the outbreak, they mobilized resources across China to bring into the Wuhan area.
So let me move to — in the last part to maybe put some of these principles a little bit in practice.
We can move to the next slide.
So in terms of preparedness, I think that we need a quantum change. We need to take the lessons much more seriously and at multiple levels. I would say that this crisis-to-crisis response is — this reactivity should be replaced by a much longer time horizon. We’re looking at much longer time horizons, very much like a story, actually, with tools that can be deployed rapidly and at scale. And that includes, again, the diagnostics, which I’ll come to at the end a little bit more; (inaudible) of sharing an analysis, and biotherapies at frontline detection capacities.
And a final comment on this, which often comes often up in discussions, can we afford diagnostics, can we afford all these things? I would raise the rhetorical questions, can we afford not to invest in preparedness in light of all the experiences we’re going through right now as we speak?
Next slide please.
So this brings me to Praesens, which as Kristel mentioned, was an initiative I took a few years ago, and really, in the aftermath of the Ebola crisis in West Africa, if you move to the next slide please — I found myself there. Maybe once I wanted to look firsthand how an outbreak is handled in real time, but also, I was there to testing a prototype Ebola test I was developing with my team at the time.
Now, for your recollection, the Ebola crisis in West Africa was the most widespread Ebola outbreak in 40 years. For the first time, it occurred in cities; for the first time in three nations; and unfortunately, more than 11,000 deaths occurred. For your information, the case fatality rate 40 percent.
Here, I look to the next slide. And it became very obvious when I was witnessing how the response unfolded with teams coming from mostly other countries, it was very, very little local infrastructure, that the first objective was detect and isolate the infected, but at some times, cases, it took several days before that could be done, and then treat the infected.
And if we move to the next slide, that let me — I couldn’t let that go, and on the way back, remembering the images of what I see there, taking time to set up; those laboratories and see some pictures here from other groups, all very well intended efforts, and they did play a crucial role in ultimately containing the outbreak. But at least my view was that we could do better, much better.
And so one of the first initiatives we took with places — if we move to the next slide please — is develop a multi-purpose mobile diagnostic platform that you see here. There’s — if you are more interested, I can definitely send you some more information. It’s a multi-terrain vehicle that encompass too some of the alternatives. It’s up and running within 15 minutes when it arrives here.
Now, unfortunately, people who manipulated the viruses, some of them became infected, and so it is very important that also the operators, technicians, scientists working with these potentially very dangerous viruses are protected. So this unit has a built-in biosafety level hood.
Importance also is autonomy, energy autonomy. And so this powers up a whole series of diagnostic systems that we put on board. Now, we’re just hearing about the challenges of the cold chain, so in such a mobile lab, the first generation, we could bring potentially cold chain capacity for more than 3,000 vaccines (inaudible) generations will be more than 13 vaccine capacity aboard, and data from the connectivity for sharing that information in real time.
Next slide. And so right now, what we did after designing this, we did a first extensive tryout for months in Senegal with a local partner because the salient element of our approach was not only innovate to assist in outbreaks, but really, empower and train — we trained over 25 people in Senegal, for instance, to operate the systems. We then donated that mobile lab and I can inform you that that mobile lab has, since a few years, involved in the fighting of several Dengue Fever outbreaks, and right now is in — is playing an important role in the Covid-19 response in the region.
Now, with support — if we move to the next slide — with support of the European authorities, the European Commission, we’re now broadening our scope, trying to put it at scale, and the Praesens program scope is visualized here, essentially for (inaudible), emergency preparedness, and response. And what you see on your top left is a response we did last year on the occasion of the — another Ebola outbreak, this time in DRC, where at some point, there was a high risk that the Goma region would become another hot spot. So we airlifted with very large (inaudible) a mobile lab to DRC. So this was an emergency response.
Right now, we are extending our model by having a mobile lab fleet on the ground and where we can do a disease surveillance and disease intelligence.
Another point — I mentioned this already, diagnostics, we are supporting and assisting in the developing of some breakthrough new diagnostics that will, in the future, allow me to do micro-testing in a much, much shorter timeframe.
And last but not least, it’s very important that we gather intelligence on these pathogens around the world.
Next slide please.
And so this is the new initiatives that we are going to roll out. As you see, our concept evolved from maybe being only an emergency response to something that is helping to bring healthcare or basic healthcare services, even to the most remote places, so that’s why you see that we are going beyond pandemic response but to general infectious disease surveillance, even cancer screening, vaccine delivery, and providing primary healthcare.
So I’ve come to the end and maybe — next slide — mention a few things. I’ll skip this — my (inaudible).
I would like to just end with highlighting again diagnostics. I’m sure you’re daily confronted with the limitations of diagnostics, and I would like to remind everybody that also in general medicine, there is really an ascent of diagnostics here, and the big trend is that we need to reinforce and strengthen really decentralization of healthcare, as we’ve seen also in this outbreak.
Next slide, please. So I’ll skip this in light of time and come to my conclusions.
So I think it’s clear that Covid-19, SARS, MERS, Ebola, and so many others are just a long list of wakeup calls, lessons, and reality checks on our preparedness and capacity to timely respond to outbreaks and pandemics. With the potential to brutally impact societies, economies, development, and security, pandemics pose more than a medical problem, more than a public health concern, and therefore, I call for a quantum change needed in our thinking, in our planning, in our organizations, in our investments, with a shift from short-lived crisis response to long-term sustainable preparedness and response.
And preparedness is key. (Inaudible) is just no blessing. Best time to act is before it happens, through the surveillance. Healthcare needs built — have building walling systems. With that, I mean that we need to escalate again the importance of infectious diseases in basic training, in basing equipment of — across the healthcare chain.
Next slide. And what you don’t measure, you can’t manage. The growing role for diagnostics in infectious disease data response, hit hard and early, with a combination of detection and appropriate diagnostics, state analysis in placing, isolation, protection, drugs, and hopefully vaccines, hopefully in future, faster vaccines.
And I want — like to end in French with this famous quote of Louis Pasteur, I would say the founder of our discipline, ” Messieurs, c’est les microbes qui auront le dernier mot. Gentlemen, it is the microbes who will have the last words.”
And I want to — next slide — thank my colleagues at the Foundation and many of the people, especially in Africa, was had the pleasure and honour of working with, and my long-time friends, Professor Peter Piot, who some of you may know, is the co-founder of — a co-discoverer of the Ebola virus, head of UNAIDS, former head of UNAIDS, and currently head of the Women’s School of Hygiene and Tropical Medicine.
And Peter wrote a very nice biography that I recommend to everybody. It’s titled “No Time to Lose”, and here, we were on one of the missions together, and he was wearing a t-shirt — you probably can’t read it, but it says, “Timing is Everything.” It’s probably — maybe another book he’s preparing
But I couldn’t agree more with this statement. So thank you very much for listening to this talk. I hope I didn’t get too much over time, but I’m open for answering any questions.