5th HLF – Lindau Lecture: The Personalized Medicine Revolution: Are We Going to Cure all Diseases and at What Price?
This is a modal window.
The media could not be loaded, either because the server or network failed or because the format is not supported.
Formal Metadata
| Title |
| |
| Title of Series | ||
| Number of Parts | 49 | |
| Author | ||
| License | No Open Access License: German copyright law applies. This film may be used for your own use but it may not be distributed via the internet or passed on to external parties. | |
| Identifiers | 10.5446/40147 (DOI) | |
| Publisher | ||
| Release Date | ||
| Language |
Content Metadata
| Subject Area | ||
| Genre | ||
| Abstract |
|
2
00:00
Internet forumAddress spaceSurface of revolutionPresentation of a groupMeeting/Interview
00:42
Bit rateInternet forumVideo gameExtreme programmingCASE <Informatik>Goodness of fitComplex (psychology)TelecommunicationDifferent (Kate Ryan album)FrustrationProteinWebsiteTask (computing)Moving averageSurface of revolutionMereologyWave packetPoint (geometry)SurgeryCellular automatonInformationSequenceBridging (networking)Mechanism designNeuroinformatikInterpreter (computing)AreaField (computer science)Digital photographySemiconductor memory2 (number)Lecture/Conference
04:52
Computer sciencePoint (geometry)Order (biology)Forcing (mathematics)FamilyPhysical systemMeeting/Interview
05:53
Video gameCurveBitRange (statistics)PredictabilityNatural numberMultiplication signMaxima and minimaExpandierender GraphMedical imagingPhysical systemFlow separationLecture/Conference
07:57
Extreme programmingFood energyRight anglePattern languageView (database)Student's t-testIntegrated development environmentMeasurementFaculty (division)NP-hardCore dumpLecture/ConferenceMeeting/Interview
09:39
Surface of revolutionArtificial neural networkGame controllerStability theoryDirection (geometry)NumberPhysical systemLimit (category theory)Network topologyLevel (video gaming)Cellular automatonMultiplication signDifferent (Kate Ryan album)PhysicalismOrder (biology)Computer-assisted translationZirkulation <Strömungsmechanik>Artificial lifeReduction of orderMereologyLecture/Conference
12:47
Surface of revolutionSurface of revolutionMultiplication signTelecommunicationObject (grammar)Different (Kate Ryan album)Lecture/Conference
13:37
MassFamilyBitOrder (biology)Chain1 (number)Complete metric spacePetri netMultiplication signOpen setTouch typingVideo gameAreaMathematicsSound effectCategory of beingMetropolitan area networkGoodness of fitPhysical systemFlock (web browser)Attribute grammarComputer virusFunctional (mathematics)NP-hardCausalityHypermediaCharacteristic polynomialLecture/Conference
20:49
Surface of revolutionEndliche ModelltheorieOrder (biology)Cellular automatonDifferent (Kate Ryan album)Row (database)Arrow of timeLink (knot theory)TouchscreenAnnihilator (ring theory)Covering spaceEndomorphismenmonoidLogic synthesisLibrary (computing)Materialization (paranormal)Product (business)Network topologySurface of revolutionParameter (computer programming)SoftwareGoodness of fitSpacetimeWater vaporArchaeological field surveyPhysical systemSoftware developerSound effectShape (magazine)Division (mathematics)RoboticsStudent's t-testCodecBit rateNeuroinformatikSequenceArtificial neural networkFitness functionSpecial unitary groupProteinNegative numberMechanism designDescriptive statisticsFamilyCategory of beingType theoryRight angleHypothesisForcing (mathematics)EvoluteSurfaceLecture/Conference
28:04
PredictionCellular automatonBit rateInternetworkingUniqueness quantificationGroup actionMechanism designSuite (music)Complex (psychology)Information technology consultingDecision theoryWebsiteRight angleFamilyLevel (video gaming)Type theoryStudent's t-testSurface of revolutionOrder (biology)Different (Kate Ryan album)Natural languageGodSurgerySequenceCharge carrierDegree (graph theory)Context awarenessCodecFundamental theorem of algebraTrailLecture/Conference
32:01
Bit rateType theoryPole (complex analysis)MeasurementSuite (music)Data storage deviceRight angleLecture/ConferenceMeeting/Interview
33:00
Bit rateStatisticsLine (geometry)FamilyTrajectoryNumberSoftware testingAddress spacePlastikkarteGroup actionAnnihilator (ring theory)CognitionStandard deviationOcean currentLecture/Conference
35:04
Bit rateStatement (computer science)Cellular automatonWater vaporTwitterLecture/Conference
36:17
BitForcing (mathematics)CausalitySequenceSampling (statistics)SurfaceCohen's kappaLecture/ConferenceMeeting/Interview
37:37
Sound effectCausalitySurface of revolutionSensitivity analysisFamilyLecture/Conference
38:55
Online helpProteinVirtual machineVideo gameDimensional analysisSurface of revolutionField (computer science)Machine visionProfil (magazine)Cellular automatonDivision (mathematics)Lecture/Conference
40:27
Bit rateGamma functionMenu (computing)Stiff equationDigital photographyNatural languageArithmetic meanInformationInformation privacyVideo gameComputer fileOrder (biology)Graph (mathematics)Multiplication signLikelihood functionStatisticsSequenceFamilySurface of revolutionLimit (category theory)Price indexComputer fontRule of inferenceLine (geometry)NeuroinformatikForcing (mathematics)State of matterLecture/Conference
44:38
Bit rateLeakInformation privacyDigital photographyLink (knot theory)Game theoryCASE <Informatik>Type theorySurgeryCharge carrierOperator (mathematics)Software testingService (economics)MereologySelf-organizationComputer scienceLikelihood functionOrder (biology)Physical systemSymbol tableDependent and independent variablesDifferent (Kate Ryan album)Multiplication signQuantum stateLecture/Conference
50:02
Internet forumLecture/Conference
Transcript: English(auto-generated)
00:01
Our next presentation is the Lindau Lecture that Countess Bettina Wernherdott mentioned yesterday in her Wacom address. And it will be given this year by Aron Shichanova, who won the Nobel Prize in chemistry in the year 2004, together with Avram Hershko and Erwin Rose, for the discovery of ubiquitin-mediated
00:25
protein degradation. And today he will talk about the personalized medicine revolution. Are we going to cure all diseases and at what price? Aron, the floor is yours.
00:48
Well, good morning everybody. I would like to start with two personal comments. One is that lecturing in Lindau is much easier for me, and the reason being that
01:00
chemistry and biology and medicine are tangible. You can see it. You may not see an electron, but you can follow an electron in a hydrogen bubble cell. You may not see a protein, but you can sequence it, you can crystallize it, you can label it and put it on a film and see it, while your world is a world of obstruction.
01:23
And for me, obstruction is very difficult because when I close my eyes, I have to see things. I find myself completely detached. I cannot do anything, I'm lost, totally lost. So now I have the task of bridging between the two worlds, and I think that part of this
01:43
difficulty is coming from my education. I am not a scientist, I am a physician. And I'm even the wrong physician, I'm surgeon by training, and surgery is all about seeing and doing. There is nothing about imagination. Of course you need to decide quickly and to use a lot of adrenaline and so on, but
02:04
it's the complete extreme of what you are doing. So thinking about what to talk to you today, I decided not to talk about our discovery on protein degradation, which is fascinating and applied to medicine in a big way these days, but rather to talk on my other side, on medicine, and mostly about the information
02:23
revolution in medicine, which is represented, I think, in the best way in the personalized medicine revolution, and we shall see how it goes. So whether we can build a bridge, basically it's a necessary bridge because there is no medicine today without informatics and without interpretation of the informatics.
02:46
The second comment that I want to personal comment is looking yesterday at the three people that passed away from your area of this field. Of course I was captured by the photo of Mariana Zarkani and read the many obituaries
03:04
that were written in her memory in recent months. I must admit I didn't understand much of what she did, but seeing the torch of life of a young person extinguished in front of your eyes and being completely helpless,
03:21
completely helpless, gives us a sense of where medicine in the extreme case is these days. The complexity of diseases that deepens and deepens as we look at it, and the fact that we are very much helpless in many diseases, in many malignancies, brain diseases, we don't
03:40
have even a clue to the mechanism not to say the therapeutic is frustrating on one hand, but on the other hand I hope that via the lecture you'll see that there is an array of hope and we are starting to take the right way. But this is, you know, seeing a young person dying in front of your eyes is the
04:01
biggest frustration that the physician, not to say a human being, can face. So let's talk about the revolution of personalized medicine. This is my city, the city of Haifa. It's a beautiful city, rolling on each side of the Mediterranean. You can see the Baha'i Garden. The Baha'is that were persecuted in Iran came to Israel bearing their leader
04:25
under a beautiful temple and converted the whole site into a beautiful rolling garden. It became a UNESCO heritage site. And the medical school where I am is just on the sea here in this very point. I'm looking from my life directly to the sea to the north and it's just gorgeous.
04:44
So personalized medicine revolution, what is it, why revolution, why now, what it entails, how it began, where it goes. So of course one point to look at it or to start it is the lifespan. If you think about people living 100 years back at the turn of the 20th century,
05:05
the average lifespan was about 50-55 and people didn't die of cancer because they didn't live long enough to have cancer. They didn't die of heart attacks because they didn't live long enough in order to get heart attack. They didn't die of Alzheimer.
05:22
The three main killers of modern medicine, heart vascular system, malignancy, brain. They died of infectious diseases. The woman died during delivery out of 10 children in the family, five could survive and the five were used mostly as a working force in the family.
05:40
Forget about the families of one or two children these days that we are teaching pianos and computer sciences and care very much about their education, just nearly 100 years ago. When we go back 4,000 years ago to the Greeks and to the Egyptian time and Chinese that were isolated from the world, the Indians, people were living on the average 30 years.
06:04
So this was the average lifetime. So it took 4,000 years to expand life's time, lifespan from about 30 to 50-55 and then it took one single century, about two and a half percent of the time to jump another 30-35 years. Now the average lifespan in the Western, in the OECD countries is about 82-84,
06:25
depends man, woman, changing, Japan is leading 86 even for woman. So one single century, we were jumping more than in four millennia. And what is it? Of course, science and technology in big way.
06:40
It's understanding diet, it's vaccinations, it's drugs, it's x-ray imaging, sewage systems, sterility, whatever you like. Take all of them together, all were developed in this magic 20th century and you have additional 30 years, 30 years to our lifespan and the curve is still going up linearly.
07:03
The United States started to go down a little bit but that's mostly due to violence, poverty in recent years but mostly it's going up in a range of several weeks a year now. So two to three weeks a year we are extending our lifespan. There was a recent prediction in nature that the upper maximum will be 115.
07:23
People doubt it. Some argue that we may be able to go farther than that. And then what about diseases? What about quality of life? The idea is not just to live, the idea is to live with high quality of life. Are we going to defeat diseases? Are new diseases going to surface that we didn't know before
07:41
like cancer and heart diseases and brain diseases were not known? Well, they were known but nobody thought that it's an epidemiological problem. At the turn of the previous century, are new diseases going to surface in the future? So are we going to cure all these diseases
08:01
and mostly are we going to pay a price for it? And by price, I mean both dollars which is going to be a problem but also other price that we may not think about but I'm going to highlight them in a big way. So if we think of medicine, many diseases are preventable.
08:21
As scientists, we don't tend to think about it if I ask because I'm teaching medicine to medical students. In my faculty, when I ask people what are the students, what do they want to do when they will grow up, most of them want to be brain surgeons, heart surgeons, all the hardcore prestigious. None of them want to be an epidemiologist but if we think about it, epidemiology and prevention of medicine
08:44
should be the way to go because this is the most logical way and the cheapest way. Think about obesity which is an epidemic in the Western world. This is a preventable disease. It's a psychological disorder. If you want to go to the extreme and think about people
09:01
that consume 5-10,000 calories a day, smoking, contamination of the environment, infectious diseases, you know, eradication of mosquitoes, the Gates Foundation that fight malaria and so on. So many of the big killers are really preventable by simple measures and by small investment.
09:21
It's just our selfishness that prevents us from going into the right places because people are people. They go after their behavioral pattern rather than after where they should go. But that's another issue of discussion of a big view of medicine. But let's go into medicine today.
09:42
Medicine today is moving in three main directions. It's moving, of course, in devices. Devices are extremely important. Engineering, actually, it's not the physicians. These are the engineers. If we think about it, you know, think about X-ray, the first Nobel Prize in 1901 in physics that went to Konrad Wilhelm Wrengen,
10:01
looking into the body without invading it, magic. And then it held for almost eight years. Eight years, one technology, until it was gradually replaced by CT scan, MRI, and our CAT scan that can also look at soft tissues. The issue with X-ray that it was either bones or nothing. Now we can look at soft tissues.
10:26
Devices, artificial valves, artificial organs, artificial joints, small cameras, drillers that can go into the arteries and clean up and drill out occlusions in the coronary arteries that feed blood into the heart itself.
10:41
So technology on one hand. Then regenerative medicine, stem cells. The promise is still not there. Hopefully it will come. But replacement of tissues that are not functioning anymore. Think about diabetes, which is probably number one disease, number one epidemic in the Western world. These are non-functioning cells in the pancreas,
11:01
in the Langerhans Island, the secret insulin. And actually if we shall be able to reprogram cell to secrete insulin, we don't have even to implant them in the pancreas. It doesn't matter. We can put them under the skin in the hand. They will secrete the hormone and the hormone will go into the circulation and reduce the glucose level. Parkinson's is a little bit different because it has to be in the brain.
11:21
Because it has to secrete a hormone that is a dopaminergic compound in the place in order to balance for the activity of the cholinergic system. Because remember, in Parkinson's we are losing control of our stability. We cannot try it. We cannot cut our food.
11:43
We cannot button up because we are... There is a dominance of one system over the other. Think about even stability. The fact that you are sitting now stable, listening or being bored to listen to me is a miracle. How does it happen that the muscles
12:01
and everything is just in place and undertone? You are not relaxed. It's undertone. It's kept undertone. Otherwise you will fall aside. So tissue engineering in stem cell has a topological problem for some of the implantations. Like if we want to put the muscle the muscle needs to be not only put in the right place
12:22
but also connected to the brain in the right way. So it will perform the right movement. But then there are tissues that have no topology like blood, like insulin secreting cells and so on. So regenerative medicine in big is the second direction. And the third direction is of course the traditional one, drugs. And we should focus mostly on drugs.
12:40
Because time limitations we need to focus. So what happened to drugs? How drugs were developed? So drugs were developed... We are talking just the 20th century. Because before the 20th century everything was completely meaningless. There were drugs, there were physicians, the barefoot physician in China all over but the communication enabled us to make
13:02
the major breakthrough. The ability to run objective clinical trials in different clinical centers in the world not knowing what one center is doing. The ability to collect data together. Actually it's not even the 20th century. The second half of the 20th century. So we are talking, we are limiting our discussion
13:22
mostly to the last 70 years or so. So the first discoveries were completely incidental. People discovered something they didn't mean to discovery but it turned out to be blockbusters. I don't have time to show you all examples. I'll show you just one example and that's aspirin. Aspirin is a drug that is being taken in tons.
13:40
It's probably the most used drug ever formed in the pharmacopeia. Many of the faces here of course of the young researchers are young but of the little bit more advanced. I'm sure that many of you, anybody has volunteered to tell me how many of you are taking aspirin daily? Oh, see, there are some hands, me too.
14:03
It's really an unbelievable drug and most people take it in order to prevent blood coagulation and heart attack. Some people like me take it in order to prevent cancer. It turned out to be one of the best chemo, cancer chemo preventive drug and it started about 4,000 years ago
14:21
when the old Egyptians noted that when they are eating, when they are chewing the willow leaves, the willow bark leaves that grew on the banks of the Nile River, the taste was very bitter but it had pain alleviating properties. It remained like that for 4,000 years
14:41
until the end of the previous century. French and German scientists took the bitterness out by acetylating it. It's a very simple compound. It's acetylsalicylic acid, very simple compound. Anybody can synthesize it in the basement and they took the bitterness away.
15:03
And then two scientists, Eiken Grun and Felix Hofmann in Bayer, in Germany, the father of one of them got rheumatoid arthritis, which is an inflammatory disease of the joints, which it's a paralyzing debilitating disease.
15:22
Again, people cannot do anything. They are painful. The joints are inflamed and they wanted to relieve the pain of the father and they read the literature and they decided to make aspirin and aspirin not only took the pain away but took the inflammation away. So they realized that they discovered
15:40
not only an analgesic drug, a pain relieving drug, but also an anti-inflammatory drug. They went to Bayer. They convinced them to make the drug officially and the rest is history. Now aspirin is being made all over the world, not only by Bayer. The patent expired years ago. And gradually what happened is the two things happened
16:02
during the last, I would say three decades. So they started in the 80s and still going on. First of all, it was discovered that aspirin prevents blood coagulation. So it's a very good drug in order to prevent heart attack. What is heart attack? Heart attack is coagulation of blood over a cholesterol wound, over a plaque,
16:22
over an atromatotic plaque in the coronary arteries that lead blood to the heart itself. So the muscle of the heart doesn't get blood and we succumb, we fail, we fall dead, or luckily not dead if the conclusion is not complete. Here you can see the patient suffering from the chest pain.
16:40
It looks like President Clinton, but it's not. So this was the first attribute, the first characteristic. The second one was the linkage that was actually discovered 120 years ago by Paul Ehrlich here in Germany about the linkage between chronic inflammation and cancer. Now people are misled to think that inflammation
17:02
is something like, wow, I have an inflammatory throat or I got wounded and there is pus. No, inflammation is a disease that many of us are suffering without knowing, liver inflammation. Many of us, millions and millions of people in the world are suffering from hepatitis, from the virus they don't know even and gradually the liver is phasing out
17:23
and losing gear. Its function, chronic intestinal inflammation, breast, prostate and people and Paul Ehrlich predicted that chronic inflammation when the tissue is all the time stimulated will lead to cancer.
17:40
The mechanistic linkage was discovered in the recent decade or the last 15 years and it turned out that if you prevent inflammation you can prevent cancer by just cutting this vicious chain in the middle and the American Cancer Society declared aspirin is the best chemopreventive.
18:03
Why all people don't take it? Because it's a drug and drug cause side effects, bleeding, gastrointestinal bleeding so it's not recommended en masse. This is always the double-edged sword of recommendation of drugs to people all over but it is recommended only to people
18:21
with family story always high susceptibility for whatever reason to take it but many people do take it because it's available on the shelf. You can buy a year supply in five dollars in CVS, Walgreens, I don't know in Germany what are the pharmacy chains
18:40
more familiar with the American ones and anyway look at this serendipity, complete serendipity no investigation no billions of dollars invested. The same story is antibiotic I don't have the time to go into antibiotic but the same story is for antibiotics that's Fleming I will just show you the serendipity in the discovery
19:00
Fleming was a microbiologist and microbiologists are using petri dishes that have agar that have a nutritious medium in order to grow the bacteria so this is the bacteria this white smear are the bacteria so he left by mistake a petri dish open on the desk and went to a vacation
19:20
it was the summer August of 1921 and when he came back he saw this white spot now the white spot is a spore of a fungi that is in the air even now here in the air that fell on the agar plate and grew because there is a very nutritious media so the spore kind of proliferated
19:40
and made the colony of the fungus but was Fleming noted that there is a hollow between the bacteria that should have grown all the way to the border of the smear there is a hollow here between the colony of the fungus and the bacteria the bacteria cannot reach cannot touch the colony of the fungus and he surmised that the fungus
20:03
secretes a material that he called antibiotics anti against bios life biology is the profession the area of life he was not a chemist it took another several years to arrange chains and hard flurry to purify penicillin and the world has changed forever
20:20
since then streptomycin came by waxman people realized that other fungi secrete other antibiotics and then synthetic antibiotics and so on and so forth so complete serendipity the guy was just looking at the dish he didn't mean he didn't investigate he didn't know anything so two major drug came by serendipity
20:41
but we cannot rely on serendipity of course not nowadays to develop drugs and we had to move to a better system and the better system the second revolution which we are still into is the high throughput brute force screening chemistry evolved side by side with biology and what happened in the two sides
21:01
is that in biology we may where biologists manage to develop disease models either in growing cells i can isolate the cancer cells from patients and grow them in the dish or in animal models i can manipulate now animals in order that they will develop disease let it be alzheimer let it be of course cells cannot imitate alzheimer or cannot imitate depression
21:21
or cannot imitate autism so some diseases can be imitated in culture cells and some diseases can be imitated by animal model as faithful as they are this is a caveat as faithful as they are so this is on the biology side on the chemistry side a chemist were able to synthesize millions of compounds
21:41
and on the synthetic pathway they left behind different intermediate materials because you move from one material to another until you get the final product so millions of compounds were accumulated many of them all the intermediate materials are useless even the end products not always being used and people say let's gather them in families
22:02
let's put them in families and if we have a model let's try to give the animal or the cells this million compound one by one we don't know the mechanism we don't have any hypotheses therefore i call it brute force and one of them will do it why?
22:20
because evolution is limited because the proteins have so many shapes and the mutated proteins gain so many shapes and one of the compounds will fit in to modulate the bad activity to inhibit it to accelerate it to do whatever the assumption turned out to be correct if you are trying millions and then of course it led to the development
22:43
lots of technologies robots that are going to the incubators take out the compounds cells that are growing bringing them together and of course computing came into the story because once you put the compound and you let the cell grow in presence of the compound then you take them to the microscope
23:01
so artificial intelligence software was developed in order to look at the cells and to say which one has effect which one you know to learn the shape of the cells the division rate and so on and so forth many parameters were put into this relatively simple I assume in your eyes software and then you have a lead that does something
23:21
and then the lead is being taken further to further experiments toxicity human trials and so on and so forth and many very good drugs came out of it and the good drugs I'll bring you one of them statins statins are cholesterol reducing drugs it's essential not to have high cholesterol level it leads again to this yellow plaques
23:42
this is for sure not President Nixon so President Clinton so you see here the yellow fatty plaque accumulating in the coronary arteries and threatens to occlude the whole space it's like rust in your pipelines of water pipelines in your home and then once the
24:00
and then on top of it the plaque also creates a wound on the surface the wound attracts blood clotting and that's the heart attack story you will always say oh the guy was jogging and he was healthy and all of a sudden he dropped dead in the streets while jogging well he had the disease for the previous 20 years but it was not diagnosed
24:20
he had this crawling occlusion coming up and up and up so statins Akira Endo a Japanese scientist worked in a pharma company he screened a library of natural products you know fungi fungal products pine tree products growing in Japan and one of them did inhibit the biosynthesis of cholesterol
24:41
and statins became a big blockbuster last year's sales were more than 40 billion dollars by different American companies I'm sure that if I'll ask you to raise your hands anybody uses statins? look just have a look and it's all the front rows of course the railroads are still not there
25:01
so statins are magic drugs not only because they are reducing cholesterol there are now claims that they are also preventing prostate cancer that they're also preventing Alzheimer's I will not go into all these links and the clinical trials that are still going on so statins by screening now screening unlike serendipity is a good way to go let's screen and screen and screen and screen
25:21
until we defeat all diseases what is the disadvantage? the disadvantage are the models we are screening mice mice are nice but they are inbred animals we turn the light at eight o'clock in the morning in the cages we turned it off at eight o'clock in the evening we feed them on cho Purina these are not human beings
25:40
human beings are vastly different from one another not only that we are men and women we are much more dissimilar to one another than we are similar think about blood infusion we cannot even transfuse blood to one another there are eight different types of blood right? A, B, O, plus and minus for each not to say a kidney transplantation or lung transplantation
26:03
this is one to ten million we need to be HLA fitting on the immune system so we are very different from one another we are different in diet we are different in genetic repertoire we are different in the sun we are different in any in every single aspect so the model is the wrong
26:21
this is one issue that we are different and then to our naivete until about 30 years ago we thought that cancer is cancer breast cancer is breast cancer it's a lump in the breast now in the ability to sequence the DNA came at the late 90s and we were able to look at it
26:42
it turns out that breast cancer is not breast cancer these are 20 different breast cancer one is derived from a mutation in the progesterone receptor and one in the estrogen receptor one in the EGF receptor one is now called triple negative it's kind of a basket to which we throw all the others that are not the other three that I mentioned to you
27:01
but in this basket they are hidden probably about 15 or 17 more and what we call the disease was basically wrongly nomenclature is a phenomenon it's a description but molecularly it's very different think about Alzheimer patient one will deteriorate like this
27:20
and one will deteriorate like this think about heart attack some people will die on the spot some people will survive five heart attack think about any disease that you want they're all variable they're all variable and we knew about it but somehow we closed our eyes we say ah you know I remember myself as a young medical student
27:41
this was not an issue even to be discussed in the medical school because we didn't know much and we said this is like okay we don't know what it is but now we do know what it is and we now have the tools also to stratify the diseases and this is the essence of the revolution of personalized medicine so now let's just go briefly into it
28:01
before we shall discuss the the the problem so it's not only personalized president obama called it also precise yes personalized precise it's the same it's not personal in the sense that there will be a drug for any mrs elizabeth changju or whatever but there will be drugs for groups of patients
28:22
that have the same molecular mechanism that is driving the disease this is the idea and in order to to diagnose it before treating we shall have to first unravel the the mechanistic reason behind the disease the pathogenic mechanism so this is the idea
28:41
because for now it's the opposite you come to the clinic and there is a breast cancer and then we don't care about the name of the patient we don't care who she is or who is or doesn't matter if the breast cancer is isolated we take it by surgery if the breast cancer is already spread by metastasis we start with chemotherapy
29:02
and then we go to surgery if possible so we don't care about the carrier of the disease we are the mirror of medicine until now was a shining towards the diagnosis of the disease now it will flip by 180 degrees into the disease in the context of the patient
29:20
so this is the major essence of this revolution and it's critical it's fundamental it's going to change the face of medicine in a very a big way so it's personalized by knowing what the patient has we are not going to limit ourselves to the disease we are going to sequence the entire dna
29:41
because you are not going to sequence the dna of the cancer of the patient you are going to sequence the entire dna and then it's going to be predictive future which tells you already the first issue here the first bioethical issue do we want to know what we are going to have don't we want to know what we are going to have
30:00
does it belong to us does it belong to the insurance agency does it belong to the government do our spouses want to know i'm just hinting to you about it so it's going to be predictive it's going to be preventive in many ways because we know what we are going to have even now but for sure in the future we shall be able to prevent it so you see it's highly implied
30:20
it's not just okay let's do the dna and most importantly it's going to be participatory i remember the days that i was a young medical student in the 60s that medicine was a very a patriarchal type of a profession trust me i'm your doctor don't ask too many questions you are a lay gun of those days
30:43
and they are gone internet of course first and foremost legal suit against companies against physicians and the complexity of the problems the physician is changing his role or her role now to become a professional consultant
31:02
kind of an advisor but not a decision making unlike it used to be 50 years ago or even 30 years ago completely different role and we are implementing it already in the medical education we are putting the physician on the side track and we are putting the patient and the family and the colleagues and what the patient have to think about him or herself
31:22
in the center on the center stage it's a very complex revolution and somehow difficult also for doctors doctors are unique unique type of creatures there is always a joke about the difference between god and doctors that god doesn't think that he's a doctor
31:43
so um so um but it's it's a joke but if you are teaching in a medical school it's not such a joke but anyway so it's going to be participatory it's going to be a dialogue and we are going to touch on all that
32:00
i want to give you just one example about this type of medicine so you will have a clue that until now really medicine was in a way very primitive actually it's still very primitive it was like what i call the pajama pajama is something unless we are very fancy royals it's something when i walk well in israel you don't take pajamas because of the of the weather
32:22
but if you're living in minnesota or in boston or on the north pole you do need something to protect yourself from the chill of the night but pajama you know you walk to a store and you ask what do they have and they tell you that they have small medium and large right you don't really measure it don't go to a tailor to make your pajama
32:43
while a suit you do go to a tailor so until now medicine was kind of a pajama one size or you know three sizes fit all and what we are going now we are going now with medicine to the tailor we are moving from the pajama to the to the suit
33:01
and the reason is exactly the same that when we are having a group of patients that are diagnosed at the same day with a certain disease and we give them the gold standard current treatment and we tell them now you're starting the road and when one of the patients are asking us or the doctor doctor tell me am i going to make it through
33:21
or am i or i'm not going to make it through the doctor tell the the patient 70 percent well for some diseases we know that they are deadly like brain cancer or most of the pancreatic cancer but but 70 percent 80 percent 10 percent doesn't matter it depends on the disease and then the patient keeps on asking but and he or she tells the doctor doctor
33:42
but i have a name and i have a family and i have an address and i have an id card what is going to be my faith the doctor tells her i don't know and what he adds if he if he wants to further elude on the problem he said listen i am 70 80 years old i've been sitting in this clinic for the last five decades i've seen two thousand like you
34:02
and the statistics is like that and therefore i'm giving you a number but the number is not sufficient not for the for the individual patient but that's what medicine could have done these days we didn't know whether the cancer will spread or it's spread already we didn't have diagnostic tools we didn't know anything we knew statistics
34:20
that's what we knew based on of course clinical data if this cancer is not spread or not metastasized or whatever or if the deterioration of the Alzheimer patient by cognitive test is going along this line the assumption that it will continue to go along this line and you can make a trajectory but otherwise the tools were awfully primitive
34:41
so patients were split and we could know only after five years or 10 years of what's happening when they split into those that were unfortunate to those that were fortunate but we didn't have any predictive tools i think that now with a with a precise medicine we are going to have much better tools
35:01
much better statistics and and so on and so forth so let me give you just one example so you will have it will come back to the beginning of my talk you will see i mean seeing is i don't know why seeing is believing has become such a strong statement for me for sure seeing is the only way of believing
35:21
so here you have two patients patient A and patient B with breast cancer so you see the cancer you see the island of the malignant cells in the biopsy you see here the islands and you can see that this island is not stained with an antibody so the browns is staining with an antibody it is against the mutated estrogen receptor
35:42
while here we try to stain but no stain it remained native so this woman woman B has a mutated estrogen receptor while woman A doesn't have it she has something else because she has cancer therefore woman A woman B can be treated with tamoxifen which is a drug to counteract the activity of the mutated estrogen receptor
36:04
while woman A treating her with tamoxifen will be a waste of money but mostly a waste of hope why to treat her with tamoxifen it's like giving her water so she should treat it with something else she may be treated with her ceptin because she may have a mutation in the egf receptor
36:21
but now it's all available we can sequence the we can take the sample and we can sequence the dna and find out what she has or and then if she has a mutation in the egf receptor then we can treat her with her ceptin by the way her ceptin made the history because it's the first biologic drug it's the first not small molecule
36:41
but an antibody against a surface molecule on the surface of the of the cancer or she may have a mutation in the progesterone receptor or unfortunately she doesn't have either of the three and she is will be classified as triple negative which is the most aggressive one because we just don't know what to do nowadays
37:01
so this just gives you a little bit of a glimpse on the stratification that there is no cancer of the breast anymore there is estrogen and progesterone and egf and nf kappa b and force and june and mink and all the others and from now on the diseases will be stratified according to their molecular cause
37:22
rather than according to the visual lesion that can be seen either in x-ray or in by by palpation or by whatever this is very primitive you should all admit so it's true not only for medicine for drugs
37:42
but it's true also for side effects still a few minutes and for side effects side effects are major problem about fourth of six of the patients in them in in american hospitals are dying because of side effect of the drugs and this is not because of negligence of the physicians most of the side effects are not known a priori
38:00
well i'm sure that you know that if you go to a hospital the physician will ask you are you sensitive to penicillin that's the only thing that we know or is there any sensitivity in your family it's meaningless we don't know every drug has side effects every drug some of them are totally unexpected and worse we don't know it a priori
38:21
we just don't know it a priori and they are all derived from the same very reason mutations in the dna so once we shall start to collect patients with the same side effect with the same reaction to the drug we shall be able to go back into the dna and to say yes the mutation in this gene is the cause and to predict a priori
38:41
so you see it's not going only to drugs it's going only for what we call adr adverse drug reaction which is a major major issue in medicine so it has many many implications this revolution but let's go to the let's go to the what we call the price and the price is by the way
39:03
i don't want you to get out of this talk with a with a naive thinking that dna is the whole story it's far away from being the whole story dna is the very base on top of the dna there is rna that is being transcribed out of the dna mostly on top of the rna there are the proteins
39:22
we are running the machines i always call i always divide life into two dimensions the horizontal dimension is reproduction of course it's dna but the but excuse me the the vertical dimension and the horizontal dimension is the proteins we are running on our proteins the muscle the hemoglobin in our blood the vision
39:42
the receptor everything the pumps on the cells it's all proteins so we have dna and we have rna and we have proteins and then we have small molecules and side by side with genomics with our ability to read our dna evolve the different fields that are all under the umbrella of omics
40:00
which is wonderful which is the transcriptomic for rna and proteomics for proteins and metabolomics for small molecules and at the end we are going to have a whole profile of the patient in front of us and a very very accurate picture of what's going on and it's going to be dynamic we should be able to monitor it as the patient is moving along the treatment
40:22
whether the treatment helps or doesn't help and so on and so forth but let me go and to the price of this revolution and the price is going to fall into two sides it's going to be technical of course because not all diseases are derived from one mutation in one gene many diseases are what we call polygenic
40:41
mostly psychological diseases but also some metabolic diseases but let's forget about technology because of time limits i want to go mostly to the bioethical issues and the bioethical issues are mostly pertaining to what you are doing and that's a data collection and privacy i'll give you i'll give you an example
41:00
i'm going to the emergency room because of chest pain chest pain is always an indication of heart problem and the doctor rules out heart attack and he comes cheerfully to me and tells me eron you don't have an heart attack but then he comes and he said i have something else to add to you because now sequencing of the dna will become a routine
41:21
it almost becomes a routine now because from the first genome that was sequenced for billion dollar in seven years now it takes about two hours and about one thousand dollars so the technology was changed we are going to solid state sequencing computers are coming to our aid the whole things have changed dramatically
41:40
and it will become routine and he said you have a mutation in apo a4 gene that is carries with it high susceptibility to alzheimer disease well high susceptibility is likelihood it's statistics still we don't know yet and what we can do about it so i'm i'm under a bombardment
42:01
i am under a bombshell in the emergency room alzheimer i came for a chest pain i don't have heart attack and i'm walking out with i said now what i'm going to do with it what this information worthwhile to whom do i talk do i talk to my wife i assume that yes okay do i talk to my children they may carry the gene what they are going to do
42:22
they are still young they have not been married yet they are in the college they are just married fiance children beginning their families do i talk to my employer will he fire me do i talk to my insurance agent you know insurance policies are being renewed yearly why should he really renew my policy
42:42
if here he has a patient with 80 percent likelihood of alzheimer so i paid for all my life when i was healthy i paid for 40 years health insurance and now when i need it out i go so so think just about what is the significance of this information to whom it belongs should the doctor hide it for me
43:01
should he tell me only the information that that there is something to do about it and keep the rest for himself or for the in the files of the hospital are the files of the hospital safe enough or they are not safe enough will the government would like to know what the citizens have would the army the military would like to know
43:22
what the what people have in order to draft the most intelligent and most fit soldiers to the military i mean it's going everywhere i want to end up because time is really running out with one photo that will give you a glimpse into it and will show you how things are going to change you see this is this is issue of genetic privacy
43:42
and what is the meaning of privacy privacy until now was something that i think belonged to me but it's not necessarily belong to me because there will be other agencies that may be interested and there will be legislation and so on and i can bring you also personal information that some that you are forced to give your information
44:02
just because of humanitarian reasons it has nothing to do with outside the forces it has to do with the helping with the kidney to my brother that is dying of a chronic kidney disease and whether i do carry the gene myself or i don't carry the gene and i can help my brother or my sister
44:20
by giving the by donating the kidney and so it's it's penetrating every layer of life it will be very difficult to put delineation marks or lines of delineation there so let me you see it's everything is everything is going wow what's going on here we are at the beginning
44:45
but okay let me go to the very last but you see that i'm afraid to to play with it because then you see it's all genetic privacy do prepare for big genome leak everything has to do with the with the keeping keeping the data
45:02
i want to end up with the with the photo of angelina jolly and angelina jolly came few years ago with a story actually i remember exactly the date it was at the beginning the middle of 2012 and then the beginning of 2013 that she's going to undergo a first operation to remove her breast
45:20
and a year later to remove her ovaries can you imagine the symbol of womanhood is going to remove the ultra symbols of womanhood i mean think about it in a in a movie industry type of of thinking and the reason is that her mother died of or was going to die at that time of breast cancer
45:43
and her aunt the sister of the mother died before ovarian cancer and she suspected that she's carrying a gene that is called BRCA1 i am attached to BRCA1 because it's part of the ubiquitin system that we discovered the side you know so this brings me the linkage but i'm going to talk about it
46:03
and she suspected that she's also carrier of the gene and therefore she's carrying in her body a ticking bomb and she's going to develop with high likelihood the disease 80% here is the end that she's going to to by 80% get breast cancer and by 40% get ovarian cancer
46:22
and breast and ovarian cancer are completely different ball games clinically breast cancer is manageable well not for all women unfortunately ovarian cancer is deadly it develops in the abdomen it takes a long time until the woman complains and once typically in 99% of the cases one is discovered it's over so she has undergone the test
46:43
and she was found to be positive and she decided to go step by step into the operation so she did a great service to women worldwide to raise alertness and it depends on the culture in the country in Israel it didn't move anything women are women they're conservative they don't care even if they carry two minds on their back
47:00
they will keep on running in America it was different it's very interesting to follow the response in different countries the culture tradition religion whatever but what about her daughters what about her daughters well she adopted but what about the daughters of other women
47:21
should she tell them again the same story maybe they are careful in what they are going to do to tell the boyfriend to tell the newlywed husband to tell the fiance to tell their children what about them now it looks frightening but let me just conclude the talk in really big ray of hope because if you think about the history of science
47:42
science have always been posing a question putting the problem and then solving it we cannot solve a problem without putting the question ahead of time and this is the same situation here it's not different we need to understand the problem in order to solve it and there is a solution already behind the corner
48:00
it's not it's not a magic solution because it has many many problems of its own but that's a technology that is called CRISPR-Cas it's a gene editing technology I'm sure all of you heard about it it's already being used for limited purposes by which we can take a mutated gene cut it away and repair it so in the case of breast cancer or ovarian cancer
48:21
these are two removable organs so Angelina and her allies were lucky because they can be subjected to complete total surgery you can remove the breast you can remove the ovaries and you are removing a preemptive you are taking a preemptive step in order to remove a bomb but in other cases we shall have to repair the genes
48:44
and this raises other ethical problems you see we are never solving the problem that's the beauty of science we shall never get bored because new problems will come what is a disease? some women will say that they want to have tall children that will be basketball players and they will discover that in their in their uterus
49:03
they are carrying little children that are going to be disastrously computer scientists so and they never dreamt of such a nightmare dream so so you see i'm exaggerating
49:21
but but what's what the the solution will come but new problems will come along with it the definition of disease will change and we'll have to cope with it and the last very sentence is that coping with this complex problem should not be put on the shoulders of scientists like you and myself we should be again the advisors
49:41
we should be the professional side this is a societal issue of clergymen legislators historians, psychologists that will all sit and look into it we are already into the problem but unfortunately society haven't started even looking into it thank you very much