The Revolution of Personalised Medicine: Its Promises and Obstacles
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Lindau Nobel Laureate Meetings313 / 340
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00:00
NobeliumQuantenchemieAlkoholische LösungQuantenchemieAlkoholische LösungWeibliche ToteNobeliumEnhancerVorlesung/Konferenz
00:37
NobeliumArzneimittelNobelpreis für ChemieVorlesung/Konferenz
01:13
NobeliumChemische ForschungArzneimittelBranntweinBesprechung/Interview
02:02
NobeliumArzneimittelCarbonatplattformBukett <Wein>Advanced glycosylation end productsVorlesung/Konferenz
02:38
NobeliumCarbonatplattformChemisches ExperimentVorlesung/Konferenz
03:18
RauschgiftArzneimittelFunktionelle GruppeChemische EigenschaftStammzelleTrennverfahrenKrebsforschungSchmerzChemotherapieKrankengeschichteRegenerative MedizinAcetylsalicylsäureIminodiethanol <2,2->PenicillinePeriodateFlussVorlesung/Konferenz
05:06
NobeliumStreptomycinPenicillineSubstrat <Boden>LokalantibiotikumResonanz-Ionisations-MassenspektrometrieMolekülbibliothekScreeningChemische ForschungSekretKrankengeschichteSymptomOrganische ChemieFettsäuremethylesterVorlesung/KonferenzChemisches Experiment
06:36
NobeliumMolekülbibliothekScreeningMolekülBukett <Wein>AllmendeKunstlederEukaryontische ZelleBleierzPathologinKrebsforschungReaktionsmechanismusSingulettzustandChemische VerbindungenLipidsenkerGesundheitsstörungPharmazieEnzymTiermodellChemische StrukturCholesterinArzneimittelBaseKlinisches ExperimentOrganische ChemieSyntheseölRauschgiftGangart <Erzlagerstätte>Ader <Geologie>BiosyntheseIndiumBiologisches MaterialVorlesung/KonferenzChemisches Experiment
08:37
StatineAbzug <Chemisches Labor>StammzelleBenetzungCholesterinInhibitorBiosyntheseGesundheitsstörungRauschgiftLipidsenkerArzneimittelKrebsforschungWeißer PhosphorKrankheitTumorFreies ElektronKlinisches ExperimentKlinische ChemieScreeningAder <Geologie>ContergankindDruckabhängigkeitWursthülleProteineWerkzeugstahlIdiotypEnergiearmes LebensmittelOrangensaftFunktionelle GruppeAbschreckenÖlVorlesung/KonferenzComputeranimation
12:12
WerkzeugstahlTranslation <Genetik>GenomProteinePosttranslationale ÄnderungDNS-SyntheseRauschgiftmiRNSWursthülleKrebsforschungRNSIdiotypAlkoholische LösungInselÖstrogenrezeptorAdeninStockfischVorlesung/KonferenzChemisches Experiment
13:04
EstranTamoxifenGeflügelfleischAlpha-1-RezeptorKrebsforschungStimulationMannoseKrebsforschungAlpha-1-RezeptorGesundheitsstörungIdiotypEstranReaktionsmechanismusRauschgiftCobaltoxideTankLinkerHope <Diamant>ÖstrogenrezeptorChemische ReaktionVorlesung/Konferenz
14:12
FormylgruppeNobeliumRauschgiftTodesursacheInterkristalline KorrosionArzneimittelChemieanlageWerkzeugstahlReglersubstanzMemory-EffektWursthülleIsopentylnitritComputeranimationVorlesung/KonferenzChemisches Experiment
15:34
PsychopharmakonKrankheitKörpergewichtHerzfrequenzvariabilitätArzneimittelChemischer ProzessHämatitModifikation <Kristallographie>RäuchernEnergiearmes LebensmittelSonnenschutzmittelAnomalie <Medizin>Elektronische ZigaretteKrankheitReaktionsmechanismusPathogeneseGenomArzneimittelFördeSetzen <Verfahrenstechnik>Energiearmes LebensmittelExplosionZwilling <Kristallographie>Vorlesung/Konferenz
16:19
GesundheitsstörungKrankheitGenomKrebsforschungEstranZellwachstumAzokupplungGesundheitsstörungAlpha-1-RezeptorIdiotypAdvanced glycosylation end productsSonnenschutzmittelWursthülleLeckageBesprechung/InterviewVorlesung/KonferenzChemisches Experiment
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LeckageSekundärstrukturDNS-SyntheseBukett <Wein>GenomGenVorlesung/KonferenzChemisches Experiment
17:49
Systemische Therapie <Pharmakologie>VerschleißGenKrebsforschungThylakoidBukett <Wein>BranntweinUbiquitinWeibliche ToteProteomanalyseGangart <Erzlagerstätte>KrankheitGesundheitsstörungVorlesung/KonferenzChemisches Experiment
20:23
ArzneimittelVorlesung/Konferenz
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ArzneimittelLipidsenkerRauschgiftFaserplatteFleischMolekülbibliothekKomplikationKlinische ChemieArzneimittelforschungCholesterinChemische ForschungStatineSpanbarkeitFettSekundärstrukturElektronische ZigaretteBaseBukett <Wein>AbszessKatalaseAntikörperPharmazieÖlResistenzPharmazeutische IndustrieMeeresspiegelTankGenomEukaryontische ZelleGenBesprechung/Interview
25:19
NobeliumKrankheitSonnenschutzmittelRauschgiftKrebsforschungSekundärstrukturSenseFunktionelle GruppeArzneimittelKaschierenHope <Diamant>IdiotypTankGenLysosomBoyle-Mariotte-GesetzSeltene KrankheitStoffpatentOrganische ChemieGesundheitsstörungVorlesung/KonferenzBesprechung/Interview
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SonnenschutzmittelStoffpatentOrganische ChemieKrankheitGangart <Erzlagerstätte>SenseQuerprofilReglersubstanzVorlesung/KonferenzChemisches ExperimentBesprechung/Interview
29:07
Organische ChemieWursthülleInterkristalline KorrosionTankInselVorlesung/KonferenzChemisches ExperimentBesprechung/Interview
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MeeresspiegelIonenbindungZuchtzielSonnenschutzmittelGenomGesundheitsstörungTeichGenVorlesung/KonferenzChemisches ExperimentBesprechung/Interview
30:59
GenArzneimittelSenseErbkrankheitBiochemikerinGesundheitsstörungIdiotypReaktionsmechanismusKrankheitDNS-SyntheseWeibliche ToteSammler <Technik>KalkammonsalpeterPeriodateHope <Diamant>Vorlesung/KonferenzBesprechung/Interview
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Aktives ZentrumMultiproteinkomplexKohlenhydratchemieMeeresspiegelKrebsforschungEukaryontische ZelleLactitolVorlesung/KonferenzBesprechung/Interview
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Eukaryontische ZelleSetzen <Verfahrenstechnik>KrebsforschungWerkzeugstahlLactitolVorlesung/KonferenzBesprechung/Interview
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NobeliumBiomarkerBasePharmazeutische IndustrieLandwirtschaftInterkristalline KorrosionMeeresspiegelElektronische ZigaretteRauschgiftArzneimittelVorlesung/Konferenz
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NobeliumMeeresspiegelBiomarkerInterkristalline KorrosionMähdrescherProteineStoffwechselwegIdiotypMetabolitKrankheitElementenhäufigkeitProteomanalyseChemisches ExperimentBesprechung/InterviewVorlesung/Konferenz
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Elektronische ZigaretteSystemische Therapie <Pharmakologie>ProteomanalyseLambicChemischer ProzessOberflächenchemieSystembiologieAssemblySpanbarkeitMannoseOrganische ChemieQuerprofilDruckabhängigkeitChemisches ExperimentBesprechung/Interview
38:45
ArzneimittelEndokrin wirksamer StoffVorlesung/KonferenzBesprechung/Interview
39:29
NobeliumVorlesung/Konferenz
Transkript: Englisch(automatisch erzeugt)
00:14
Hi, I'm Elena G. Levine. I'm President of Quantum Success Solutions. I'm a speaker, a science writer, author of a book called Networking for Nerds,
00:22
and I'm especially honored to be here today as a consultant to the Lindau Nobel Laureate meetings. Some of you may have recognized me from the fight to the death that occurred yesterday, but today we're going to have a really exciting Agora talk. I'm super excited for it, and I know you're going to be too. I'd like to introduce our speaker, Aaron Chikunova.
00:42
He won the Nobel Prize in Chemistry in 2004. He's not going to talk about the work that he did. However, he's going to talk about something that touches all of us and will continue to touch all of us, the issue of personalized medicine. Aaron, please. Okay. Good morning, everybody.
01:05
Actually, the background to my talk was laid already in the panel, and much was said already, which will ease our work and our discussion. And what I want to do with you today is divide it into two.
01:21
One is the first part, which will be the short one, will be me presenting you with a little bit of a frame of the issue of personalized medicine, the physical part, and then the bioethical, the obstacles, the technological and the bioethical one. But then most of it will be devoted to you, to elicit
01:40
a discussion and questions and so on and so forth, as far as we can discuss it. I will try to answer some of the questions. Other people, participants who are here, will do it in the free agora spirit. So, just to give you an introduction, this is my city,
02:01
Haifa. It's a beautiful city, sitting on the slopes of the Carmel Mountain on the very east side of the Mediterranean, and on the very left, upper side, you see a white building. This is the medical school where we are. It's one faculty of many of the Technion, the Israel Institute of Technology, which is residing on the other side of the mountain.
02:20
The medical school traditionally is always near the teaching hospital, and we have a big teaching hospital nearby. So, what is the Agora? Why, it's a new organization, it's a new platform here in Lindau, the Agora Talk, launched this year. So the Agora is an old Greek institution
02:41
established in Athens more than 5,000 years ago, and it has many meanings, but mostly it was a meeting place, or later on it became a market place. And interestingly, the Athenian Agora existed for almost 5,000 years, until very recently. And it was
03:00
destroyed and reconstructed, destroyed and reconstructed, and had many shapes in it. And you can see the original one, which was beautiful, and now you can see the remnants, which are below one of the temples in the excavation in Athens. So it's a, and I think that it's a nice name that was given to this platform.
03:20
Because it's really something that we should keep open, discuss, rather than give a panel lecture or so on. You have enough of panel lectures. So, personalized medicine. Medicine is moving today in several directions. As you all know, it's moving in devices, you know, MRI and functional MRI, and robotic surgery. So that's the
03:44
engineering part of medicine, which is critically important. Then it's moving in another direction, which is parallel, which is regenerative medicine. Stem cell biology, transplantation, and so on. And then it's moving in the traditional direction, which is drug development. And if you look at drug development, mostly in the 20th century, there were, I would say,
04:04
three revolutions. That's my view. It's based on history, but other people can have another view. So the first revolution was the era of incidental discoveries. Many drugs, which are still blockbusters, were discovered by coincidence. I will not go to aspirin, which is probably the most used drug in the history of the pharmacological
04:24
industry. I think that it's being consumed nowadays in tons. In tons, it was discovered basically by the old Egyptians, not as aspirin, but 4,000 years ago, they chewed the willow barks on the banks of the Nile River. It was extremely bitter, but on the other hand, they notified that it
04:43
has also pain alleviating properties. And then it was developed in the 19th and 20th century to become anti-fever, anti-pain, and more recently, anti-inflammatory, and probably the best cancer chemopreventive drug. So you see how things are going. And it was complete serendipity, nothing about the billion dollars that are invested nowadays in
05:03
drug development. Penicillin, another serendipity. Sir Alexander Fleming, you can see here the dish, it's not the original dish, I will not go into it, was a microbiologist, forgot a Petri dish on the table for the weekend. It was August of 1921, I think, came back a few days later
05:24
and he saw that a spore of a fungus fell on the nutritious media of the Petri dish, grew into this, say, you see, white colony. But then he noted something that I suspect that many other people, including myself, would not have noted, and that there is a halo between the bacterial smear and the white colony.
05:44
And what he surmised, that the fungus secretes a material that he called antibiotics, anti-against, bioslive, that somehow deters the bacteria from approaching all the way to the very border, to the very rim of the fungal
06:00
of the fungal colony. He was not a chemist, he took another almost 15 years, Ernst Chain and Howard Flory purified the penicillin from this fungus and the rest is history. Then Selman Waxman realized that other fungi may secrete, other antibiotic material
06:20
and streptomycin came to the world and the avalanche started and we are living in a completely different world. Serendipity, not any investment, nothing. A little bit more sophisticated than aspirin, but nevertheless about the same. Then came the era that we are still in, which is the era of high-throat brute force screening of large libraries.
06:41
This era evolved because of merging of two fields, one hand synthetic organic chemistry, the ability of chemists to synthesize numerous compounds after multiple steps, having numerous intermediates sitting in libraries of a common structural base and families and so on. One hand, the other hand is development of
07:04
disease models, like the ability to culture cancer cells or cells that will secrete, that will generate a lot of cholesterol and so on, and then even animal models. And then people say let's let's marry the two fields, let's take this million compounds without even knowing the mechanism, without thinking about mechanism
07:24
develop machineries and even artificial intelligence devices and screen the molecules one by one by one by one for the purpose of inhibiting the pathological process. And the idea was that there are so many structures in nature and one of the million will fit
07:43
into the structure of the enzyme that has to be inhibited or activated it doesn't matter, and this is still not a drug, it's just a lead and then we shall improve it and go to clinical trials and more advanced animal studies but the beginning is always a screen, and if you go to the screening facilities of big pharma companies you will see these beautiful screening facilities
08:03
you will see millions of compounds are sitting in trays of 384 little wells, the robot is coming, taking a sample, bringing it to the tissue to the culture cells, then the next day the culture cells are going to the microscope, no hands involved, the microscope is looking at them and say okay there is a change in the culture, the cells don't grow
08:23
if it's anti-cancer or doing something, doesn't matter and then start of course the whole story. But this is a brute force mechanism. And then people started to ask themselves and one of the drugs that was developed like this, statins again it's a multi-billion dollar drug, it's an inhibitor of cholesterol
08:43
biosynthesis that is used in order to inhibit the accumulation of cholesterol in the coronary arteries, you see there the occluded coronary arteries this is the vessel that brings blood to the heart itself, and so on and so forth but nowadays we know that statins are doing many more things than just inhibiting cholesterol, it's being used also for, probably will be used
09:03
also for preventing Alzheimer's with some patients that have some apolipoprotein mutation, carrier protein mutation, and so on, now people talk about prostate cancer, many drugs are now being repurposed it's very interesting, I'm not going to talk about the repurposing of drugs Thalidomide is one example of those, but we shall not talk about it
09:22
so this drug was developed based on screen. But then people realized now we are going into our revolution, the double the four P's revolution, the personalized predictive preventive and participatory that we all talked about during the panel and it came from the notion that basically
09:42
or the complaint of physicians and mostly patients that the outcome of any treatment is basically unknown, when we are giving a drug to the patient, even if there is a diagnosis, one patient will respond favorably, there will be a very significant effect, the other one will have a mild effect, let's say that the blood pressure will go
10:03
down only, you know, not to the full extent but only partially, some will not respond at all, some will develop side effects, so, and the side effects can be not only rash they can be really even fatal side effects, and we'll talk about the side effects some will develop beneficial effects and side effects side by side, then
10:22
the doctor will have to weigh which is worse and what to do with the drug, whether to take the patient of the drug, and it's unpredicted, it's really unpredicted we don't know what is the outcome of the treatment, we don't know you know, when we talk about diseases, we think that the disease has one definition, but every patient has his or her
10:42
own disease, because the disease exists in a completely different genetic environment, environmentally circumstances, diet, anything is different, so breast cancer is a tumor in the breast, but probably it's not similar in one woman to another woman to another woman, the same
11:02
for prostate cancer in men, and therefore we see this variety, if we take a group of patients they are colored with green, blue, and yellow and we send them to the gold standard treatment, some of them will end up dying and suffering along the route, and some of them will be treated and will go back to the community, and that's in the case that the disease is curable, there are diseases that are not
11:22
curable at all, but we are not talking about it, so the question is the prediction the patient complains, they say to the doctor, doctor, tell me, what is my chances of being here with you in your office five years from now, and the doctor tells the patient 50%, and the patient said, doctor this is statistics, tell me what is the chances of me
11:42
Mr. Robert X, Mr., I don't know, to be here with you I have a name, I have a family, I'm living in some place, what are my chances and doctor said, I don't know, it's only statistics, how do I know? Because I've been sitting in this clinic for the last 25 years, I've seen 2,000 like you and this is the statistics, so I read the literature, or the clinical trials say it
12:02
and anything like that, and this is intolerable in science, it's intolerable in medicine, and specifically it's intolerable for the patients and, but we didn't have tools, and the tools came later on and the tools as of course, it started with the human genome, 2,000, nature unraveling of the human genome, but this was just the beginning
12:22
because we all talked about it, DNA is only the very beginning, top of DNA there is RNA and microRNA in proteins, and million different post-translational modifications, and the picture is much vaster, much bigger than just the genome, but the idea is profiling the patient, identifying the cause, and then if there is a drug
12:42
we shall treat the patient with the appropriate drug, and if there isn't a drug, at least we know that some of the patients have a new mutation and the drug should be developed so it's a road map, it's not only for treating the patient, but it's also for future patients in case we don't have a solution for the current patient, because we are going to discover new diseases, and I can bring you just one, which is breast cancer
13:02
again, so here you can see two biopsies from breast cancer patients, one is stained immunohistochemically for a mutated estrogen receptor, the other is not, two women, you can see the cancer itself, you can see the island, so of course the woman that is stained the woman on the right can be treated with tamoxifen, which is an anti-estrogen receptor
13:22
or mutated estrogen receptor, the left one will be useless to treat her with tamoxifen, because it will be not only a waste of money, but it will be a waste of hope, it will not help her at all, so maybe she has something else, and something else can be a mutation in the EGF receptor so she should be treated with Herceptin, we call it molecular stratifying
13:42
and the third one should be a problem in the progesterone receptor, and people predict now that there will be 20 different breast cancers, so calling breast cancer is not a disease anymore, it's a name for a lump in the breast, that's all what it is, it's not a disease, the disease should be defined by the cause, by the underlying mechanism that is driving
14:03
the disease, and each of them should be treated completely differently and so here we are in this revolution, and the same for ADR, for adverse drug reaction, it's a major issue, fatal ADR appeared to be between 4th and 6th leading cause of death in the USA, we are
14:23
killing patients by inducing them adverse drug effect, because we know nothing about it, you give a drug to the patient and the next hour he can die of anaphylactic shock, we are typically asking the patient, I remember, do you have sensitivity to penicillin, yes that's the only thing we know, and that depends on the memory of the patient that when he was a kid
14:43
and the mother gave him penicillin, he developed a rash, but that's all where it goes far, that's how far it goes, we don't know whether we are sensitive and basically we are sensitive to anything in the world, any pollen, any cat, any dog, anything, there is one person that walks on the face of earth that is sensitive to something that is in the air, on the plant
15:02
on the sea, anywhere, so we need also tools to predict ADR because it's serious, side effects in the hospital, I'm not talking about negligence of the medical crew, which is also happening, that's another issue of quality control in the hospital, I'm talking about unexpected side effects to drugs that
15:23
are unpredictable and there is lack of tools to predict them, so this is also an issue of personalised medicine, of fitting the drug to the patient, the drug can be perfect but it may kill the patient at the same time OK, so let's go now towards the end and of course the variety between us is the basis
15:43
of all this story, men and women, tall and low, diet, genetic repertoire, anything that makes us, actually there are not two people on the face of earth that are identical to one another, not even identical twins, because they change along their life, epigenetic, so not even identical twins, not one
16:03
single person on the face of earth is identical to any other person that walks on the same planet, so we should remember it and therefore no wonder that we respond differently to the different pathogenetic mechanisms of diseases and of course to different drugs, so let's go to the problems that we face, so human
16:22
genome then building banks of diseases sequencing 5000 breast cancer in order to classify them into progesterone and estrogen and growth and growth factor receptor mutations and NF kappa b signaling, whatever it is and the same for any diseases, it cover
16:42
about 95%, I will not go into the statistics, 5000 of each disease cover about 95, we leave some rare cases aside because it will be very difficult to cover, you know the cost effectiveness is very high to cover everything and then we come to the problems and the problem is
17:02
of course a leak of the information, we talked about it and I'm not going to tell you a lot about it but we are going to raise it in the question, to whom belong the information how private it is, especially information that pertains to the future remember when I'm going to sequence your DNA or my DNA I'm going not only to know about current situation but I may be able to
17:22
know about the future and that we talked about it, this is something that is not only dangerous because some other people may know about it like the insurance company, the employer, it has family implications it has psychological implications on the patient himself and so on and so forth so we talked about it and we will raise it, so be prepared for the big genome leak
17:41
it's one problem and of course many bio-ethical issues, I'm not going to mention all of them but just bring this beautiful lady Angelina Jolley that came few years ago with the announcement that she is going to remove initially her breast, a year later her ovaries because it was discovered that she is the carrying of the BRCA1 mutated gene
18:02
BRCA1 happens to be a ligase of the ubiquitin system, that's something completely else, but it carries about 50 to 80% susceptibility for breast cancer about 35% to 40% susceptibility to ovarian cancer and breast and ovarian are completely two different ball games, breast I wouldn't say curable
18:22
but it's mostly curable, appropriate diagnosis, routine checks ovarian develops somewhere in the hidden, in the lumen of the abdomen in the peritoneum when mostly discovered it's lost, most of the patient, more than 95 of the women are dying of the disease, it's a death penalty, so it's a different
18:42
and she decided to take pre-emptive steps, remove the ticking bomb from her body which is very nice and also made a huge public service, but then of course the same questions come Angelina Jolley is Angelina Jolley, I'm not Angelina Jolley and people have families, what does it mean for the family
19:02
to the children, should we tell the children, shouldn't we tell the children that there may also be a risk, Angelina Jolley is grown up, she has her own children, some adopted one, the young one in the family haven't started their life, what does it mean for them should they know, shouldn't they know, how should they know, what do they tell their spouses so there are many questions that are coming up here
19:21
and all should be discussed and I believe that if we look again and that will be my concluding statement, we look again at the whole problem, they are technological problems we are far away from solving them, but they will be solved, technology is always easy, you know of course the profiling, proteomic is still
19:41
not there, we still are far away from understanding all the PTMs and obviously analysing them, but this will be solved, but technology always running ahead of moral, bio-ethical and societal, religious, cultural issues always, we are ahead of it, and then the big societal religious, bio-ethical issues and the financial issues are also
20:01
part of it, should it be to whom it will be affordable, to whom it will be accessible, to whom not, we just had a wonderful breakfast today about problems of health provision systems in Africa, so you know the world is a complex one, challenging one and I think that I leave it off here and the rest of the time
20:22
is yours, in the agora spirit. So I'm sure you have tons of questions, so why don't we just jump right into it yes, we have a question, we're going to give you a mic, so hold on a second
20:46
Thanks so much, it was great, I really enjoyed, my question is about the cost so personal medicine costs a lot of money, how much do you think we should personalize the medicine to afford it? Well it's very difficult to predict, you know I'm not in the industry, so I'm a little bit
21:03
of an amateur, so if anybody else in the audience has an answer, more knowledge base, I really welcome it, but there are some predictions to be made, first of all look at sequencing, initially sequencing was costing like, I remember in my days when I was first sequencing my own genes, was like two or three
21:23
dollars a base, now it's like 0.001 cent a base and you can make a whole human genome for nothing, few thousand dollars and it will go down even further because the sequencing method was changing from chemical sequencing to solid state sequencing which is all electronic, so things are changing, the market is changing according to
21:43
the demand, there will be also more demand for machines and reagents and so the market will react accordingly, you cannot sell to a patient something I can tell you that typically in the market, in the clinical market, I'm not talking about treatment, I'm talking about diagnosis, you know the most expensive one in the market should be at the range of five hundred to
22:03
two thousand dollars, any examination, CAT scan, MRI and so on treatment is something else, so things will go down there is no doubt about it, the problem will be the pharma companies and I mentioned it during the panel and that's the problem that for them the blockbuster era is going to be ending
22:22
for now there are many drugs that are blockbuster drugs, whether they help the patient or not, the patient don't have, take statins for example, statins are being sold for cholesterol, it's the only drug in the world, it's the second drug there is a second drug that just came to the market recently in the last few years it's an antibody which is called PCKS9, but statins are the
22:43
major drug, they are sold for billions and billions of dollars of years for many years and the companies, but it's clear that many of the patients are not benefiting from it, either the cholesterol reduction is not sufficient or they develop side effects mostly myositis, the drug affects the muscles and some of the complications are fatal, you get myositis
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that will kill you, and the rest are painful muscles and so on but people buy it, they say okay the cholesterol will be reduced by ten percent and nevertheless go to the pharmacy, put hundred dollars and have the cholesterol reduced and then I avoid eating eggs, I don't know what and fat meat or whatever, but people take it because there is no choice
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the pharma companies are aware that there are twenty different reasons for hypercholesterolemia, I don't know, twenty, but we know that there are several of those once all the reasons will be dissected by the sequencing and by patient population, the market will be sliced, so statins will be used to treat only a section
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of the hypercholesterolemic patients and the rest will be treated by other drugs that will be developed, so the companies are going not only to lose money on a blockbuster drug, but to invest money in the development of new drugs and they are reluctant to do it, and the pharma companies are all private they have CEOs, they have board of directors, they have shares in the market
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and all of the CEO has to do at the end of the year is to show the board of directors that the share went up that's all, otherwise he's out of the game, so the pharma companies are really, and they are reluctant to do it, there is nobody to tell them we talked about antibiotics, I don't know if Ada talked to you about the antibiotic market they don't want to develop antibiotics, it's short living
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you take it for some sore throat or some abscess even for ten days then the companies are interested in one thing, that you take the drug for the rest of your life and the rest of your life will be long that's what they are interested in, they are interested in chronically sold drugs they are not interested in drugs that you are taking for ten days and a year later
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the bacteria will develop resistant to the drug and it will be out of the market anyway so that's it, so it's hard to predict but it's there and it's there to be with us there is no way to stop it and for the good it's a major revolution, it may seem critical but it's really going to change the face of medicine
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and to the good, we need to deal with the price of it the price meaning not only the dollar price but the other prices that we talked about but it's here to be with us and we have to solve the problems that will arise along the way
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yes? You mentioned quite nicely that we are very different, each and every single person so how personalised are we going to go with the medicine? It's a little bit of misleading name I think
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I think that President Obama coined it a little bit better, he called it a nice medicine because it's more precise the name personalised is a little bit misleading in the sense that people are asking me are doctors to be more humane, they are going to class to talk to us? No, they are going to be colder, they are going to talk in a more difficult jargon
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less understandable jargon and so on and so forth, so it's not going to be that person it's going to be even worse than now, or people are asking me how many drugs we can develop will it be personal to each of us? Of course not there will not be drug on your name, hopefully you will not have to use drug anyway, but there will not be drug on my name
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but diseases will be stratified, that's the issue and the issue of the sequencing of the gene bank of breast cancer glioblastoma, pancreatic cancer, whether it's RAS mutation or MYC mutation or whatever is going to be stratified and there will be groups of any disease now and initially drugs will be developed for the big groups
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and then maybe orphan diseases are also suffering today a lot disease that has 200 patients in the United States, forget about it, nobody will touch it no commercial company will touch it, they are not going to develop and I can tell you many storage diseases, lysosomal storage diseases are orphan, so there will be no drug for each patient
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that walks on the face of the earth, but there will be drugs for the big groups initially and then probably it will crawl also to smaller group and what the borderline of the market, because the companies always want to know how the market works for them, they want to know how much money they can make out of the drug, if they have a patent for 20 years
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let's work under ideal conditions the border of how the number of the patients in the country, the United States patients are better insured than in Uganda for example, so all this will be coming into consideration, I hope that also philanthropic organizations will come into it in order to help the margins
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and so on and so forth, but that's how people envision it and from the technical side of things, how are you going to intercalate all the information you showed nicely in the diagram that there are a lot of factors that influence it's a good one, there is a call now, you know we are just getting not we, I'm not there, so I'm like you in that sense
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people are calling now for sharing data there is a big call for sharing data, mostly the big organization, the EU is one of the organizations that is really very strong on sharing data of all the banks, the NIH and the NCI in the United States doing the same, the idea is that all the banks will share their data
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so companies and patients and health providing organizations will be able to use it, it's not going to be your data and so on and so forth of course actually there will be even conditions on patenting that some grants you will not be able to patent the information for your benefit, if you agree to get the grant then the information will become public immediately and so on
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so people are taking steps in order to share it, there is not yet what we talked in the morning, a world government that will look after it and will organize it, I like the term, world government that will faithfully and sincerely
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control us, but it's not there yet but people are starting to talk about it very seriously But this data is coming from the West really, I mean the organizations are mostly Western, how applicable is that? Not only, there is a big organization that is doing things in hepatitis C and D and E in inflicted regions like in South East Asia
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Indonesia and so on and so forth, it's not so true mostly from the West but also from the East side and true the East was a little bit always behind Africa is a major issue, sensitivity to malaria major issue, Africa has 90% of all malaria cases
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in the world, the rest is a little bit in Cambodia, Thailand South East Asia, so yeah it's a problem but I think that it's on the desk I would say, yes, maybe other ones
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to participate, I mean I really So my question is a little bit linked to my colleagues question Wonderful. I'm just thinking about this as a delivery at the point of delivery where a patient comes in you've got to know if they're malnourished, are they anemic, so many factors
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that you've got to take into account in addition to their genome as well as their epigenome I'm just wondering how clinicians will deal with this at the point of care, because it's going to become incredibly complex, so it's going to be different from a patient comes
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in with disease X, you open the big book, you know how many milligrams per kilogram to give and it's standardized, what checks and bonds are we going to put in place to make sure that everyone still at least gets the same standard or level of care and how do we avoid inaccuracies and how do you weigh the difference
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so which gene a person has versus their anemia or their lupus or anything else that's going on, how are we going to deal with that at the point of care? Well let me start and then I really want other people to relate to it. First of all we shouldn't be blinded personalized medicine is not medicine, it's one section of medicine
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road accidents and violence are not under the personalized medicine they should be stopped by other means, you know killing people by rifles or by cannons and road accidents and just physical violence and I can bring you many other examples, there are many environmental diseases and so on, so not everything is
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personalized medicine, of course the distinction should be made but many diseases that we do think are only environmental, they are nevertheless personalized, in the sense that you and I can have infected by the flu virus, you will develop a very light disease and I will die out of it because of immune compromise, because
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of genetic, because of entry mechanism of the virus into the cell, because of different reasons, so we should really be able to increase our knowledge to the extent that we know what is really belonging to this arena and what does not belong and do it and it will be at the beginning will be very difficult
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the beginning will be very difficult, what I hope is that and it will be based on fortunately or unfortunately the only experimental animal that will give us the best information is called the human being we cannot use rabbits here, we cannot use mice and it will be information that will be
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accumulated and therefore handling of the database and sharing them is critically important I think that initially sequencing and some molecular profiling will be becoming routine, like I don't know, even in Africa, even in any underdeveloped country that a blood test is not being made, so DNA sequencing
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once it will be cheap enough will be added to the blood testing and biochemistry it will be done too and then the information will come, so the analysis will be done and then people will relate some mutation to some disease, to some susceptibility, to some death once this is being done then we can handle it in a more
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but I would say that the initial period, I cannot predict how long it's going to take will be of collecting information and stratifying the disease and mostly the difficult cases, you know it's not just the genetic diseases that have direct mutation but how a genetic
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variation even affects the disease course and they ultimate the final final outcome, aging and so on and so forth once we know that I think we'll be smarter, so in the beginning the first stage is going to be data collection
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yes, other people want to comment on this one, there are physicians around MD PhDs, let's make the discussion a little bit more, but the question still remains whether AI can handle that level of complexity, I've spoken to
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computational biologists and they say well, algorithms can be built but the complexities get more complex so hopefully they are going to be accelerating on that side too, so that's how it's going to be handled I think It's true, just read an article about the importance of AI
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in analyzing what we call the liquid biopsies which is the new way to diagnose and to predict cancer for example, circulating DNA, circulating cancer cells that are there in tiny amounts and then what does it mean that you have a little signal on top of the huge noise how significant it is and how can it tell you, so we certainly
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will need this type of tools Other comments, not a question, any comments to this one important question, yes, go ahead So I'm a science communicator from the pharma industry actually and you described
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it as if there is a high reluctance of the pharma industry to really dive into the personalization thing and my impression is different and so we asked our companies, the research based pharmaceutical companies how many of your projects are really also analyzing
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possibilities, options for personalization and they said it's roughly 40% of our projects where we do it and most of the time we end up not having any biomarkers in our hands, so in the end the drugs get approved without biomarkers
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which can guide the personalization, but it's not for the lack of trying and maybe and sometimes it works that you get the biomarkers later and then you can really personalize the use of this drug. Probably the issue of the biomarker which is critically important, not only for diagnosis but also
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for following up the treatment because the biomarker should go down is critical but maybe it's a problem of the lack of sensitivity that now the biomarkers are still with the current instrumentation below the level of detection but in time, as you said, they will come they will improve and the sensitivity will improve
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I think we have time for one or two more questions
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Hello, you have nicely described different layers of omics data, so we have transcriptomics, proteomics and so on so when it comes to combination or integration of those I guess it's difficult to correlate a mutation with a protein abundance and then later on because of the PTMs with a metabolite
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so my question would be what would you suggest that we first investigate the different profiling data separately and then combine them via statistics or machine learning algorithms or we should really look into biology, into networks or pathways and then see if these are predictive
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I think that luckily the scientific community is totally disorganized really, I am meaning it and everybody is doing whatever they want and at the end it assembles. So some people develop matiasman develop proteomic technologies, other people develop genomic, other people like you heard yesterday are doing AI
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and machine learning to know how many neurons you need in your brain to remember that Donald Trump was elected to be President of the United States and so it's coming from different directions and at the end people are and then you see it with your own eyes, then a new era of science is coming to the surface and that's system
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biology, until ten years ago nobody talked about system biology, so these are people that are integrating all the information, the hubs and the robustness of the hub and so on and so forth. So I trust the scientists to do it and I much prefer this chaotic disorganized, somebody at the end will come and organize, the supervisor is, let's say Valiant called
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yesterday will come and organize us. Well and maybe these will be the supervisors of tomorrow so that... Right, right. And since we have only a minute left I'd like to ask you about regarding the young scientists that are in the audience, what can they do to position themselves for success, to be contributors, to be leaders to be disruptors and innovators in this field
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quote unquote of personalized medicine for the future? I never consult people what to do, I mean it's not, I think that in general if you want to be successful in whatever you're doing, you want to be a ballet dancer, you want to be an architect, you want to be anything that you want to be do something that you are passionate about, that you really love
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to do and that your gut feeling tells you that you are good at. And the gut feeling is an important part because sometimes you don't... Awfully important. Yes, absolutely. The gut feeling versus the background noise of your friends and your family members. Right. And that gut can change with the gut microbiota, right? Right.
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Let's thank Aaron, this was a wonderful Agora talk, thank you.