It's a pleasure to be here in Edinburgh, Scotland, the birthplace of the needle and syringe. Less than a mile from here in this direction, in 1853 a Scotsman filed his very first patent on the needle and syringe. His name was Alexander Wood, and it was at the Royal College of Physicians. This is the patent. What blows my mind when I look at it even today is that it looks almost identical to the needle in use today. Yet, it's 160 years old.
Zadovoljstvo je biti danas ovdje u Edinburghu, Škotskoj, mjestu gdje su nastale igla i šprica. Manje od kilometra i pol u ovom smjeru 1853. godine jedan je Škot zatražio svoj prvi patent na iglu i špricu. Njegovo ime je Alexander Wood, i to se dogodilo na Kraljevskom koledžu liječnika. Ovo je patent. Ono što me zapanjuje čak i danas kad ga pogledam jest činjenica da izgleda skoro identično kao igla koju koristimo danas. A patent je star 160 godina.
So we turn to the field of vaccines. Most vaccines are delivered with the needle and syringe, this 160-year-old technology. And credit where it's due -- on many levels, vaccines are a successful technology. After clean water and sanitation, vaccines are the one technology that has increased our life span the most. That's a pretty hard act to beat.
Ali osvrnimo se malo na područje cjepiva. Većina cjepiva se vrši ubodom igle ili šprice, 160 godina starom tehnologijom. Ali moramo joj odati veliko priznanje -- na mnogo razina, cjepiva su vrlo uspješna tehnologija. Uz čistu vodu i sustav kanalizacije, cjepiva su tehnologija koja je najviše pridonijela produžetku životnog vijeka ljudi. Teško je to nadmašiti.
But just like any other technology, vaccines have their shortcomings, and the needle and syringe is a key part within that narrative -- this old technology. So let's start with the obvious: Many of us don't like the needle and syringe. I share that view. However, 20 percent of the population have a thing called needle phobia. That's more than disliking the needle; that is actively avoiding being vaccinated because of needle phobia. And that's problematic in terms of the rollout of vaccines.
Ali kao i svaka druga tehnologija cjepiva imaju svoje nedostatke, a igla i šprica su ključni dio ove priče -- ova zastarjela tehnologija. Pa počnimo s očitim: mnogi ljudi ne vole igle i šprice. I ja se u potpunosti slažem s tim stavom. Međutim 20 posto populacije pati od nečega što se zove fobija od igala. To je jače od osjećaja da ne volite igle; to znači da aktivno izbjegavate cijepljenje upravo zbog fobije od igala. I to je problematično u smislu primjene cjepiva.
Now, related to this is another key issue, which is needlestick injuries. And the WHO has figures that suggest about 1.3 million deaths per year take place due to cross-contamination with needlestick injuries. These are early deaths that take place.
Drugi ključan problem vezan uz ovo jesu ozljede prouzročene iglom. Statistika Svjetske zdrastvene organizacije ukazuje da negdje oko 1,3 milijuna ljudi umre godišnje zbog kontaminacije koja se dogodi preko ozljeda prouzrokovanih iglom. Sve su ovo preuranjene smrti.
Now, these are two things that you probably may have heard of, but there are two other shortcomings of the needle and syringe you may not have heard about. One is it could be holding back the next generation of vaccines in terms of their immune responses. And the second is that it could be responsible for the problem of the cold chain that I'll tell you about as well.
Ovo su dvije stvari za koje ste zasigurno čuli, ali postoje dva nedostatka igle i šprice za koje možda niste čuli. Jedan od njih je taj što bi igla i šprica mogle usporiti razvoj sljedeće generacije cjepiva po pitanju njihovog imunosnog odgovora. A drugi nedostatak je taj što bi takva tehnologija mogla biti odgovorna za problem hladnog lanca o kojem ću vam također govoriti.
I'm going to tell you about some work that my team and I are doing in Australia at the University of Queensland on a technology designed to tackle those four problems. And that technology is called the Nanopatch. Now, this is a specimen of the Nanopatch. To the naked eye it just looks like a square smaller than a postage stamp, but under a microscope what you see are thousands of tiny projections that are invisible to the human eye. And there's about 4,000 projections on this particular square compared to the needle. And I've designed those projections to serve a key role, which is to work with the skin's immune system. So that's a very important function tied in with the Nanopatch.
Govorit ću vam o radu na kojem radim zajedno sa svojim timom u Australiji na Sveučilištu Queensland i to na tehnologiji koja bi se upravo trebala baviti s ova četiri problema. I ta se tehnologija zove Nanoflaster. Ovo je primjerak Nanoflastera. Kada ga pogledamo golim okom, izgleda nam poput kvadrata manjeg od poštanske marke, ali ako ga pogledate ispod mikroskopa vidjeti ćete tisuću sićušnih ispupčenja koje su nevidljive ljudskom oku. Oko 4.000 ispupčenja se nalazi na ovom kvadratu kad ga usporedimo s iglom. I dizajnirao sam ta ispupčenja kako bi poslužili ključnoj svrsi, a to je da rade zajedno s imunosnim sustavom kože. I to je vrlo važna funkcija povezana s Nanoflasterom.
Now we make the Nanopatch with a technique called deep reactive ion etching. And this particular technique is one that's been borrowed from the semiconductor industry, and therefore is low cost and can be rolled out in large numbers.
Danas proizvodimo Nanoflaster tehnikom koja se zove duboko reaktivno ionsko graviranje I ta specifična tehnika je preuzeta iz područja industrije poluvodiča, i zbog toga je jeftina te može imati široku primjenu.
Now we dry-coat vaccines to the projections of the Nanopatch and apply it to the skin. Now, the simplest form of application is using our finger, but our finger has some limitations, so we've devised an applicator. And it's a very simple device -- you could call it a sophisticated finger. It's a spring-operated device. What we do is when we apply the Nanopatch to the skin as so -- (Click) -- immediately a few things happen. So firstly, the projections on the Nanopatch breach through the tough outer layer and the vaccine is very quickly released -- within less than a minute, in fact. Then we can take the Nanopatch off and discard it. And indeed we can make a reuse of the applicator itself.
Sad nanosimo sloj cjepiva u suhom stanju na ispupčenja Nanoflastera i tada stavljamo Nanoflaster na kožu. Najednostavniji način primjene jest nanošenje prstima ali i naši prsti imaju ograničenja, pa smo osmislili aplikator. I to je vrlo jednostavan mehanizam -- mogli bismo ga nazvati sofisticiranim prstom. To je mehanizam koji radi na principu opruge. Što se događa kada nanesemo Nanoflaster na kožu -- (Klik) -- odmah se dogodi nekoliko stvari. Prvo, ispupčenja na Nanoflasteru probijaju čvrsti vanjski sloj kože i cjepivo se brzo otpušta -- i sve to zapravo traje manje od jedne minute. Tada možemo skinuti Nanoflaster i baciti ga. Ali sami aplikator možemo ponovno koristiti.
So that gives you an idea of the Nanopatch, and immediately you can see some key advantages. We've talked about it being needle-free -- these are projections that you can't even see -- and, of course, we get around the needle phobia issue as well.
Ovo bi vam trebalo otprilike dati ideju o tome kako radi Nanoflaster, i odmah možete uočiti neke ključne prednosti. Rekli smo već kako smo iz primjene izbacili iglu -- ovdje se radi o ispupčenjima koje ne možete vidjeti -- a tako, naravno, uspješno rješavamo problem fobije od igle.
Now, if we take a step back and think about these other two really important advantages: One is improved immune responses through delivery, and the second is getting rid of the cold chain.
Sad malo stanimo i promislimo o druge dvije, vrlo važne, prednosti: jedna je poboljšani imunosni odgovor zahvaljujući provedbi, a druga je ta što se rješavamo hladnog lanca.
So let's start with the first one, this immunogenicity idea. It takes a little while to get our heads around, but I'll try to explain it in simple terms. So I'll take a step back and explain to you how vaccines work in a simple way. So vaccines work by introducing into our body a thing called an antigen which is a safe form of a germ. Now that safe germ, that antigen, tricks our body into mounting an immune response, learning and remembering how to deal with intruders. When the real intruder comes along the body quickly mounts an immune response to deal with that vaccine and neutralizes the infection. So it does that well.
Počnimo s prvom prednošću, s idejom imunogenosti. Trebat će vam malo vremena da shvatite ovaj pojam ali pokušat ću pojednostavniti. Vratit ću se korak unazad i objasniti vam na jednostavan način kako cjepiva funkcioniraju. Dakle cjepiva funkcioniraju tako da u tijelo unosimo tvar koje se zove antigen koja je zapravo sigurni oblik bakterije. Tada ta sigurna bakterija, taj antigen na prevaru izaziva imunosnu reakciju našeg tijela koji tako uči i pamti kako postupati s uljezima. Kada pravi uljez dođe tijelo brzo stvori imunosnu reakciju kako bi se suočilo s cjepivom i neutralizirao infekciju. I to radi dobro.
Now, the way it's done today with the needle and syringe, most vaccines are delivered that way -- with this old technology and the needle. But it could be argued that the needle is holding back our immune responses; it's missing our immune sweet spot in the skin. To describe this idea, we need to take a journey through the skin, starting with one of those projections and applying the Nanopatch to the skin. And we see this kind of data. Now, this is real data -- that thing that we can see there is one projection from the Nanopatch that's been applied to the skin and those colors are different layers. Now, to give you an idea of scale, if the needle was shown here, it would be too big. It would be 10 times bigger than the size of that screen, going 10 times deeper as well. It's off the grid entirely. You can see immediately that we have those projections in the skin. That red layer is a tough outer layer of dead skin, but the brown layer and the magenta layer are jammed full of immune cells. As one example, in the brown layer there's a certain type of cell called a Langerhans cell -- every square millimeter of our body is jammed full of those Langerhans cells, those immune cells, and there's others shown as well that we haven't stained in this image. But you can immediately see that the Nanopatch achieves that penetration indeed. We target thousands upon thousands of these particular cells just residing within a hair's width of the surface of the skin.
Danas se to radi iglom i špricom, većina cjepiva djeluje na taj način -- koristeći ovu staru tehnologiju i iglu. Ali moglo bi se argumentirano tvrditi da igla zapravo sputava našu imunosnu reakciju; ona promašuje imunosno najučinkovitiji dio na našoj koži. Kako bih vam predočio ovu ideju, moramo krenuti na putovanje kroz kožu, krenut ćemo od jednog ispupčenja i nanošenja Nanoflastera na kožu. I vidimo ovu vrstu podataka. Sada, ovo su stvarni podatci -- ovo što možemo vidjeti tamo jest ispupčenje s Nanoflastera koji je nanesen na kožu a ove boje predstavljaju različite slojeve. Kako bih vam dao nekakvu predodžbu o proporcijama, kad bismo ovdje prikazali iglu, ona bi bila prevelika. Ona bi bila 10 puta veća od veličine ovog ekrana, a također bi i prodirala 10 puta dublje. Usporedba nije čak ni moguća. Možete odmah primijetiti da su ispupčenja u koži. Ovaj crveni sloj je čvrsti vanjski sloj mrtve kože, ali smeđi sloj i magenta sloj su pretrpani imunosnim stanicama. Naprimjer, u smeđem sloju se nalazi određena vrsta stanice koju nazivamo Langerhans stanica -- svaki četvorni milimetar našeg tijela je pretrpan ovim Langerhans stanicama, imunosnim stanica, a prikazane su i druge stanice koje nismo zabilježili na ovoj slici. Ali možete odmah vidjeti da Nanoflaster uspijeva zaista prodrijeti. Mi ciljamo na tisuće i tisuće ovih stanica koje se nalaze unutar površinskog sloja kože tankog poput dlake.
Now, as the guy that's invented this thing and designed it to do that, I found that exciting. But so what? So what if you've targeted cells? In the world of vaccines, what does that mean? The world of vaccines is getting better. It's getting more systematic. However, you still don't really know if a vaccine is going to work until you roll your sleeves up and vaccinate and wait. It's a gambler's game even today.
Kao čovjek koji je smislio ovu napravu i dizajnirao je da čini sve ovo, za mene je to uzbudljivo. Pa što? Pa što ako smo naciljali stanice? U svijetu cjepiva, što to zapravo znači? Svijet cjepiva postaje bolji. Postaje sustavniji. Međutim, još uvijek ne možete zaista znati hoće li cjepivo raditi, sve dok ne zavrnete rukave, cijepite se i čekate. To je kocka čak i danas.
So, we had to do that gamble. We obtained an influenza vaccine, we applied it to our Nanopatches and we applied the Nanopatches to the skin, and we waited -- and this is in the live animal. We waited a month, and this is what we found out. This is a data slide showing the immune responses that we've generated with a Nanopatch compared to the needle and syringe into muscle. So on the horizontal axis we have the dose shown in nanograms. On the vertical axis we have the immune response generated, and that dashed line indicates the protection threshold. If we're above that line it's considered protective; if we're below that line it's not. So the red line is mostly below that curve and indeed there's only one point that is achieved with the needle that's protective, and that's with a high dose of 6,000 nanograms. But notice immediately the distinctly different curve that we achieve with the blue line. That's what's achieved with the Nanopatch; the delivered dose of the Nanopatch is a completely different immunogenicity curve. That's a real fresh opportunity. Suddenly we have a brand new lever in the world of vaccines. We can push it one way, where we can take a vaccine that works but is too expensive and can get protection with a hundredth of the dose compared to the needle. That can take a vaccine that's suddenly 10 dollars down to 10 cents, and that's particularly important within the developing world.
Ali morali smo se kockati. Uzeli smo cjepivo za gripu i nanijeli ga na naš Nanoflaster a Nanoflaster smo nanijeli na kožu i onda smo čekali -- i sve smo to napravili na živoj životinji. Čekali smo mjesec dana i ovo smo otkrili. Ovo je prikaz podataka koji pokazuju imunosnu reakciju koju smo dobili Nanoflasterom u usporedbi s onom koju smo dobili ubodom igle i šprice u mišić. Na horizontalnoj osi je naznačena doza u nanogramima. Na vertikalnoj osi je prikazana dobivena imunosna reakcija, a isprekidana linija pokazuje prag zaštitnosti cjepiva. Ako smo iznad tog praga, cjepivo se smatra zaštitnim; a ako smo ispod te linije, onda nije. Crvena linija se većim dijelom nalazi ispod te krivulje i zapravo samo je jedna točka dobivena metodom igle zaštitna i to s visokom dozom od 6.000 nanograma, ali primjetit ćete odmah bitno drugačiju krivulju koji smo postigli plavom linijom. To smo postigli Nanoflasterom; korištena doza kod Nanoflastera je prikazana posve drugačijom krivuljom imunogenosti. To je prava, sviježa prilika. Odjednom imamo potpuno novu polugu u svijetu cjepiva. Možemo je gurnuti u tom smjeru da uzmemo cjepivo koje je djelotvorno ali preskupo i možemo dobiti zaštitu uzimajući samo stoti dio doze koji bismo trebali uzeti kad bismo koristili iglu. To bi moglo dovesti do toga da cjepivo koje košta 10$ padne na samo10 centi, a to je pogotovo važno za zemlje u razvoju.
But there's another angle to this as well -- you can take vaccines that currently don't work and get them over that line and get them protective. And certainly in the world of vaccines that can be important. Let's consider the big three: HIV, malaria, tuberculosis. They're responsible for about 7 million deaths per year, and there is no adequate vaccination method for any of those. So potentially, with this new lever that we have with the Nanopatch, we can help make that happen. We can push that lever to help get those candidate vaccines over the line. Now, of course, we've worked within my lab with many other vaccines that have attained similar responses and similar curves to this, what we've achieved with influenza.
Ali postoji i druga strana svega ovoga -- možete uzeti cjepiva koja nisu djelotvorna i dovesti ih iznad te linije i učiniti ih zaštitnima. A naravno u svijetu cjepiva ovo može biti vrlo važno. Pogledajmo veliku trojku: HIV, malariju i tuberkulozu. Ove bolesti su odgovorne za otprilike 7 milijuna smrti godišnje, i ne postoji primjerena metoda cijepljenja za bilo koju od njih. Ovom novom polugom koju imamo zahvaljujući Nanoflasteru možemo potencijalno postići i to. Možemo gurnuti tu polugu kako bismo pomogli potencijalnim cjepivima prijeći tu liniju. Radili smo, naravno, u mom laboratoriju s mnogo drugih cjepiva koja su postigla reakcije i krivulje slične ovoj koju smo dobili koristeći cjepivo protiv gripe.
I'd like to now switch to talk about another key shortcoming of today's vaccines, and that is the need to maintain the cold chain. As the name suggests -- the cold chain -- it's the requirements of keeping a vaccine right from production all the way through to when the vaccine is applied, to keep it refrigerated. Now, that presents some logistical challenges but we have ways to do it. This is a slightly extreme case in point but it helps illustrate the logistical challenges, in particular in resource-poor settings, of what's required to get vaccines refrigerated and maintain the cold chain. If the vaccine is too warm the vaccine breaks down, but interestingly it can be too cold and the vaccine can break down as well.
Sada bih želio malo govoriti o drugom ključnom nedostatku suvremenih cjepiva, a to je potreba da se održava hladni lanac. Kao što i samo ime kaže -- hladni lanac -- to je zapravo potreba da se cjepivo od proizvodnje pa sve do trenutka kad se primjenjuje, čuva zamrznuto. i tu se javljaju neki logistički izazovi ali imamo načine kako i to uspješno riješiti. Ovo je malo ekstremniji primjer ali može prikazati logističke izazove, posebno u okolini koja je siromašna resursima, što je sve potrebno kako bi se cjepiva zamrznula i kako bi se održao hladni lanac. Cjepivo se kvari ako je izloženo previsokim temperaturama ali zanimljivo je da cjepivo može biti izloženo i preniskim temperaturama i da se opet može pokvariti.
Now, the stakes are very high. The WHO estimates that within Africa, up to half the vaccines used there are considered to not be working properly because at some point the cold chain has fallen over. So it's a big problem, and it's tied in with the needle and syringe because it's a liquid form vaccine, and when it's liquid it needs the refrigeration.
Sada, ulozi su vrlo visoki. Svjetska zdravstvena organizacija procjenjuje da u Africi čak polovica cjepiva koja se tamo koristi najvjerojatnije nije djelotvorna jer se upravo u jednom trenutku prekinuo hladni lanac . Tako da je to veliki problem a usko je povezan s korištenjem igle i šprice zato što se tu radi o tekućem obliku cjepiva, a u tom slučaju cjepivo treba zamrzavati.
A key attribute of our Nanopatch is that the vaccine is dry, and when it's dry it doesn't need refrigeration. Within my lab we've shown that we can keep the vaccine stored at 23 degrees Celsius for more than a year without any loss in activity at all. That's an important improvement. (Applause) We're delighted about it as well. And the thing about it is that we have well and truly proven the Nanopatch within the laboratory setting. And as a scientist, I love that and I love science. However, as an engineer, as a biomedical engineer and also as a human being, I'm not going to be satisfied until we've rolled this thing out, taken it out of the lab and got it to people in large numbers and particularly the people that need it the most.
Ključna osobina našeg Nanoflastera jest ta da se cjepivo nalazi u suhom stanju a kad je suho, ne treba zamrzavanje. U laboratoriju smo pokazali da možemo skladištiti cjepivo na temperaturi od 23°C i to u razdoblju dužem od godinu dana bez gubitka razine aktivnosti. To je vrlo važan napredak. (Pljesak) I mi smo oduševljeni time. A što je najbitnije u svemu ovome jest da smo zaista dokazali učinkovitost Nanoflastera u laboratorijskom okruženju. I kao znanstvenik volim to i volim znanost. Međutim, kao inžinjer, kao biomedicinski inžinjer i kao ljudsko biće neću biti zadovoljan dok ne zakotrljamo ovaj projekt i ne izađemo iz laboratorija te učinimo ovo dostupno ljudima i to pogotovo ljudima kojima je to najpotrebnije.
So we've commenced this particular journey, and we've commenced this journey in an unusual way. We've started with Papua New Guinea.
Tako da smo započeli ovo putovanje a započeli smo ga na vrlo neobičan način. Počeli smo u Papui Novoj Gvineji.
Now, Papua New Guinea is an example of a developing world country. It's about the same size as France, but it suffers from many of the key barriers existing within the world of today's vaccines. There's the logistics: Within this country there are only 800 refrigerators to keep vaccines chilled. Many of them are old, like this one in Port Moresby, many of them are breaking down and many are not in the Highlands where they are required. That's a challenge. But also, Papua New Guinea has the world's highest incidence of HPV, human papillomavirus, the cervical cancer [risk factor]. Yet, that vaccine is not available in large numbers because it's too expensive. So for those two reasons, with the attributes of the Nanopatch, we've got into the field and worked with the Nanopatch, and taken it to Papua New Guinea and we'll be following that up shortly.
Papua Nova Gvineja je primjer zemlje u razvoju. Otprilike je iste veličine kao i Francuska ali tu smo naišli na mnoge ključne prepreke koje postoje u svijetu suvremenih cjepiva. Tu je logistika: u ovoj zemlji postoji samo 800 hladnjaka u kojima se čuvaju cjepiva. Mnogi su stari, poput onoga u Port Moresbyju, mnogi se kvare, a mnogi nisu dostupni u Gorju gdje su prijeko potrebni. To je izazov. Ali također Papua Nova Gvineja ima najveću stopu pojave HPV-a, humanog papilloma virusa, raka grlića maternice [činitelj rizika] u svijetu. Ipak to cjepivo nije dostupno u velikim količinama jer je preskupo. Iz ta dva razloga, te zahvaljujući karakterstikama Nanoflastera, počeli smo se baviti ovim i raditi s Nanoflasterom te smo ga odnijeli u Papuu Novu Gvineju a uskoro ćemo provesti i praćenje rezultata.
Now, doing this kind of work is not easy. It's challenging, but there's nothing else in the world I'd rather be doing. And as we look ahead I'd like to share with you a thought: It's the thought of a future where the 17 million deaths per year that we currently have due to infectious disease is a historical footnote. And it's a historical footnote that has been achieved by improved, radically improved vaccines. Now standing here today in front of you at the birthplace of the needle and syringe, a device that's 160 years old, I'm presenting to you an alternative approach that could really help make that happen -- and it's the Nanopatch with its attributes of being needle-free, pain-free, the ability for removing the cold chain and improving the immunogenicity. Thank you. (Applause)
Nije lako obavljati ovu vrstu posla. Izazovno je, ali nema toga na svijetu što bih radije radio. I dok gledamo prema budućnosti, podijelio bih s vama ovu misao: To je ideja o budućnosti u kojoj je 17 milijuna smrtnih slučajeva koje godišnje imamo kao posljedicu zaraznih bolesti samo povijesna fusnota. Povijesna fusnota koju smo uspjeli ostvariti poboljšanim, radikalno poboljšanim cjepivima. I dok danas stojim pred vama na mjestu gdje su nastale igla i šprica, izumi koji su 160 godina stari, predstavljam vam novi pristup kojim bi se to moglo i ostvariti -- a to je upravo Nanoflaster, kojemu su glavne osobine to što smo se riješili igle i boli, te mogućnost da se izbjegne potreba za hladnim lancem i da se poboljša imunogenost. Hvala. (Pljesak.)