I want to tell you guys something about neuroscience. I'm a physicist by training. About three years ago, I left physics to come and try to understand how the brain works. And this is what I found. Lots of people are working on depression. And that's really good, depression is something that we really want to understand.
Saya ingin memberitahu Anda tentang ilmu saraf. Saya seorang fisikawan dalam pelatihan. Tiga tahun yang lalu, saya meninggalkan fisika. dan beralih untuk mempelajari cara kerja otak. Inilah yang saya temukan. Banyak orang meneliti masalah depresi. Dan itu sangat bagus, karena kita ingin memahami segala sesuatu tentang depresi.
Here's how you do it: you take a jar and you fill it up, about halfway, with water. And then you take a mouse, and you put the mouse in the jar, OK? And the mouse swims around for a little while and then at some point, the mouse gets tired and decides to stop swimming. And when it stops swimming, that's depression. OK? And I'm from theoretical physics, so I'm used to people making very sophisticated mathematical models to precisely describe physical phenomena, so when I saw that this is the model for depression, I though to myself, "Oh my God, we have a lot of work to do."
Cara untuk memahaminya : Ambil toples, lalu isi separuhnya dengan air. Kemudian ambil seekor tikus, dan masukkan tikus itu ke dalam toples. Tikus itu akan berenang beberapa saat pada akhirnya, tikus itu kelelahan dan berhenti berenang. Ketika tikus itu berhenti berenang, saat itulah ia depresi. Oke? Saya mendalami fisika teoritis, jadi saya biasanya membuat suatu pemodelan matematika yang rumit untuk mendeskripsikan fenomena fisika secara detail. Jadi, saat melihat ini untuk memodelkannya Saya berpikir, "Ya Tuhan, banyak sekali tugas kami."
(Laughter)
(Tertawa)
But this is a kind of general problem in neuroscience. So for example, take emotion. Lots of people want to understand emotion. But you can't study emotion in mice or monkeys because you can't ask them how they're feeling or what they're experiencing. So instead, people who want to understand emotion, typically end up studying what's called motivated behavior, which is code for "what the mouse does when it really, really wants cheese." OK, I could go on and on. I mean, the point is, the NIH spends about 5.5 billion dollars a year on neuroscience research. And yet there have been almost no significant improvements in outcomes for patients with brain diseases in the past 40 years. And I think a lot of that is basically due to the fact that mice might be OK as a model for cancer or diabetes, but the mouse brain is just not sophisticated enough to reproduce human psychology or human brain disease. OK?
Ini adalah masalah umum dalam ilmu saraf. Misalnya adalah emosi. Banyak orang ingin mempelajari tentang emosi. Tapi Anda tak bisa mempelajari emosi pada tikus atau monyet karena Anda tak bisa tanyakan apa yang mereka rasakan atau alami. Sebaliknya, mereka yang mempelajari itu, mereka akhirnya mempelajari perilaku motivasi, misalnya, "apa yang akan dilakukan tikus jika ia sangat menginginkan keju." Banyak contoh lainnya. Maksud saya, intinya adalah NIH menghabiskan 5,5 miliar dolar setahun untuk penelitian ilmu saraf. Tapi, hampir tidak ada kemajuan pada pasien penyakit otak dalam 40 tahun ini. Dan saya pikir pada dasarnya ini karena tikus biasanya dijadikan model untuk kanker atau diabetes tetapi otak tikus kurang canggih untuk mewakili psikologis atau penyakit otak manusia. Oke?
So if the mouse models are so bad, why are we still using them? Well, it basically boils down to this: the brain is made up of neurons which are these little cells that send electrical signals to each other. If you want to understand how the brain works, you have to be able to measure the electrical activity of these neurons. But to do that, you have to get really close to the neurons with some kind of electrical recording device or a microscope. And so you can do that in mice and you can do it in monkeys, because you can physically put things into their brain but for some reason we still can't do that in humans, OK? So instead, we've invented all these proxies. So the most popular one is probably this, functional MRI, fMRI, which allows you to make these pretty pictures like this, that show which parts of your brain light up when you're engaged in different activities. But this is a proxy. You're not actually measuring neural activity here. What you're doing is you're measuring, essentially, like, blood flow in the brain. Where there's more blood. It's actually where there's more oxygen, but you get the idea, OK?
Jadi, jika model tikus sangat buruk, mengapa kami masih menggunakannya? Sebenarnya, dasarnya adalah otak terdiri dari neuron, yaitu sel-sel yang saling mengirim sinyal listrik. Jika ingin memahami cara kerja otak, Anda harus mengukur aktivitas listrik neuron. Untuk melakukan itu, Anda harus berinteraksi dengan neuron menggunakan alat perekam listrik atau mikroskop. Jadi Anda bisa menggunakannya pada tikus atau monyet karena Anda bisa masukkan benda ke otak mereka tapi kami masih tidak bisa melakukannya pada manusia. Jadi kami menciptakan semua ini. yang paling umum adalah MRI dan fMRI yang bisa menghasilkan gambar menarik seperti ini, yang menunjukkan bagian otak yang bekerja saat Anda melakukan berbagai aktivitas. Ini hanyalah . Anda tidak mengukur aktivitas saraf. Yang Anda lakukan adalah mengukur aliran darah di otak. Saat lebih banyak darah Sebenarnya ada lebih banyak oksigen. Anda mengerti, kan? Hal lain yang bisa Anda lakukan adalah
The other thing that you can do is you can do this -- electroencephalography -- you can put these electrodes on your head, OK? And then you can measure your brain waves. And here, you're actually measuring electrical activity. But you're not measuring the activity of neurons. You're measuring these electrical currents, sloshing back and forth in your brain. So the point is just that these technologies that we have are really measuring the wrong thing. Because, for most of the diseases that we want to understand -- like, Parkinson's is the classic example. In Parkinson's, there's one particular kind of neuron deep in your brain that is responsible for the disease, and these technologies just don't have the resolution that you need to get at that. And so that's why we're still stuck with the animals. Not that anyone wants to be studying depression by putting mice into jars, right? It's just that there's this pervasive sense that it's not possible to look at the activity of neurons in healthy humans.
yang dapat Anda pakai di kepala, Lalu Anda dapat mengukur gelombang otak. Sebenarnya Anda mengukur aktivitas listrik. Tapi Anda tidak mengukur aktivitas neuron. Yang Anda ukur adalah arus listrik yang mengalir bolak balik di otak Anda. Sesungguhnya teknik ini mengukur hal yang tidak tepat. Sebab, sebagian besar penyakit yang ingin kita pahami, misalnya Parkinson, Pada Parkinson, ada satu jenis neuron otak yang bertanggung jawab pada penyakit ini, dan teknologi belum mampu memecahkan masalah itu. Karena itulah kami masih memakai hewan. Bukan berarti kami mempelajari depresi dengan menaruh tikus di toples, kan? Hanya saja, kami tidak mungkin meneliti aktivitas neuron pada manusia sehat.
So here's what I want to do. I want to take you into the future. To have a look at one way in which I think it could potentially be possible. And I want to preface this by saying, I don't have all the details. So I'm just going to provide you with a kind of outline. But we're going to go the year 2100. Now what does the year 2100 look like? Well, to start with, the climate is a bit warmer that what you're used to.
Jadi inilah yang akan saya lakukan. Bayangkan masa depan. Menurut saya, ada satu cara yang mungkin untuk dapat dilakukan. Saya belum punya semua detailnya. Jadi saya akan ceritakan garis besarnya saja. Kita akan menuju tahun 2100. Seperti apa tahun 2100? Pertama, iklimnya lebih panas.
(Laughter)
(Tertawa)
And that robotic vacuum cleaner that you know and love went through a few generations, and the improvements were not always so good.
Dan robot penghisap debu andalan Anda, mengalami beberapa perubahan, dan perubahannya tidak begitu baik. (Tertawa)
(Laughter)
It was not always for the better. But actually, in the year 2100 most things are surprisingly recognizable. It's just the brain is totally different. For example, in the year 2100, we understand the root causes of Alzheimer's. So we can deliver targeted genetic therapies or drugs to stop the degenerative process before it begins. So how did we do it? Well, there were essentially three steps. The first step was that we had to figure out some way to get electrical connections through the skull so we could measure the electrical activity of neurons. And not only that, it had to be easy and risk-free. Something that basically anyone would be OK with, like getting a piercing. Because back in 2017, the only way that we knew of to get through the skull was to drill these holes the size of quarters. You would never let someone do that to you.
Tidak selalu menjadi lebih baik. Namun sebenarnya, di tahun 2100, perubahan-perubahannya dapat dikenali. Otak mengalami perubahan besar. Misalnya pada 2100, kita tahu penyebab Alzheimer. Jadi dapat kita obati dengan terapi atau obat genetik untuk mencegah proses degeneratif. Bagaimana caranya? Pada dasarnya ada tiga langkah. Pertama, kami harus mencari cara untuk mendapatkan arus listrik melalui tengkorak sehingga kita dapat mengukur aktivitas listrik neuron. Tak hanya itu, cara itu harus mudah dan tanpa resiko. Suatu hal yang semua orang tak keberatan, seperti menindik telinga. Karena pada tahun 2017, satu-satunya cara untuk menembus tengkorak adalah dengan mengebor lubang kecil. Anda pasti tak akan mau mengalaminya.
So in the 2020s, people began to experiment -- rather than drilling these gigantic holes, drilling microscopic holes, no thicker than a piece of hair. And the idea here was really for diagnosis -- there are lots of times in the diagnosis of brain disorders when you would like to be able to look at the neural activity beneath the skull and being able to drill these microscopic holes would make that much easier for the patient. In the end, it would be like getting a shot. You just go in and you sit down and there's a thing that comes down on your head, and a momentary sting and then it's done, and you can go back about your day. So we're eventually able to do it using lasers to drill the holes. And with the lasers, it was fast and extremely reliable, you couldn't even tell the holes were there, any more than you could tell that one of your hairs was missing. And I know it might sound crazy, using lasers to drill holes in your skull, but back in 2017, people were OK with surgeons shooting lasers into their eyes for corrective surgery So when you're already here, it's not that big of a step. OK?
Jadi pada tahun 2020, orang-orang mulai bereksperimen, bukan dengan membuat lubang raksasa, tapi mengebor lubang mikroskopis, yang lebih tipis dari sehelai rambut. Ide ini sebenarnya untuk diagnosis, banyak penyakit otak yang perlu diamati aktivitas saraf di dalam tengkoraknya dan melubanginya dengan saangat kecil akan memudahkannya, termasuk bagi pasien. Ini rasanya seperti disuntik. Anda masuk ke ruangan dan duduk, dan sesuatu masuk ke kepala Anda ada rasa sakit sesaat lalu selesai, dan Anda beraktivitas seperti biasa. Jadi, kami melakukannya dengan menggunakan laser untuk mengebor. Dengan laser, semua cepat dan mudah, bahkan Anda tak bisa melihat bekas lubangnya, seperti Anda tak sadar ada satu rambut yang hilang. Memang ini terdengar gila, menggunakan laser untuk melubangi tengkorak, tetapi pada tahun 2017, ahli bedah menggunakan laser untuk mengoperasi mata. Jadi itu bukanlah masalah besar. Oke?
So the next step, that happened in the 2030s, was that it's not just about getting through the skull. To measure the activity of neurons, you have to actually make it into the brain tissue itself. And the risk, whenever you put something into the brain tissue, is essentially that of stroke. That you would hit a blood vessel and burst it, and that causes a stroke. So, by the mid 2030s, we had invented these flexible probes that were capable of going around blood vessels, rather than through them. And thus, we could put huge batteries of these probes into the brains of patients and record from thousands of their neurons without any risk to them. And what we discovered, sort of to our surprise, is that the neurons that we could identify were not responding to things like ideas or emotion, which was what we had expected. They were mostly responding to things like Jennifer Aniston or Halle Berry or Justin Trudeau. I mean --
Jadi langkah berikutnya pada tahun 2030an, bukan hanya menembus tengkorak. Untuk mengukur aktivitas neuron, kita harus masuk ke jaringan otak. Risikonya, jika sesuatu dimasukkan ke jaringan otak hal itu dapat menyebabkan stroke. Bisa saja kena pembuluh darah dan menyebabkan stroke. Jadi pada pertengahan tahun 2030, kami punya suatu alat yang elastis yang dapat mengelilingi pembuluh darah, bukan menembusnya. Alat ini menggunakan baterai, yang dimasukkan ke dalam otak pasien, lalu merekam ribuan neuron tanpa adanya risiko. Hal yang mengejutkan dalam penemuan kami adalah neuron yang kami identifikasi tidak merespons ide atau emosi, yang semula menjadi dugaan kami. Mereka merespons hal-hal seperti Jennifer Aniston atau Halle Berry atau Justin Trudeau Maksud saya--
(Laughter)
(Tertawa)
In hindsight, we shouldn't have been that surprised. I mean, what do your neurons spend most of their time thinking about?
Sebenarnya itu tidak terlalu mengejutkan. Maksud saya, apa yang sering dipikirkan oleh neuron-neuron Anda?
(Laughter)
(Tertawa)
But really, the point is that this technology enabled us to begin studying neuroscience in individuals. So much like the transition to genetics, at the single cell level, we started to study neuroscience, at the single human level.
Tapi intinya adalah teknologi ini mampu mempelajari ilmu saraf pada manusia. Sama seperti transisi genetika pada tingkat sel, kita bisa mempelajari ilmu saraf pada tingkat manusia.
But we weren't quite there yet. Because these technologies were still restricted to medical applications, which meant that we were studying sick brains, not healthy brains. Because no matter how safe your technology is, you can't stick something into someone's brain for research purposes. They have to want it. And why would they want it? Because as soon as you have an electrical connection to the brain, you can use it to hook the brain up to a computer. Oh, well, you know, the general public was very skeptical at first. I mean, who wants to hook their brain up to their computers? Well just imagine being able to send an email with a thought.
Tapi kami belum sampai ke sana. Karena teknologi ini terbatas pada bidang medis, artinya kami mempelajari otak yang sakit, bukan otak yang sehat. Karena seaman apa pun teknologi, Anda tak bisa memasukkan sesuatu ke otak seseorang hanya untuk penelitian. Mereka harus sukarela. Lalu mengapa mereka harus bersedia? Karena sambungan listrik di otak akan dihubungkan ke komputer. Tentu saja, awalnya, publik sangat meragukannya. Siapa yang mau otaknya dihubungkan ke komputer? Bayangkan saja menulis email hanya dengan memikirkannya.
(Laughter)
(Tertawa)
Imagine being able to take a picture with your eyes, OK?
Bayangkan Anda bisa memotret dengan menggunakan mata.
(Laughter)
(Tertawa)
Imagine never forgetting anything anymore, because anything that you choose to remember will be stored permanently on a hard drive somewhere, able to be recalled at will.
Bayangkan Anda tidak akan pernah melupakan apapun karena semua ingatan tersimpan permanen pada perangkat, yang bisa diakses kapan saja. (Tertawa)
(Laughter)
Di sini batasnya antara kegilaan dan khayalan yang tak jelas.
The line here between crazy and visionary was never quite clear. But the systems were safe. So when the FDA decided to deregulate these laser-drilling systems, in 2043, commercial demand just exploded. People started signing their emails, "Please excuse any typos. Sent from my brain."
Tapi sistemnya aman. Ketika FDA menghapuskan sistem pengeboran laser, pada tahun 2043, permintaan penggunaannya akan melonjak. Orang-orang akan mencantumkan email mereka dengan "Maaf bila ada salah pengetikan. Dikirim dari otak saya." (Tertawa)
(Laughter)
Para penjual bermunculan menawarkan penghubung saraf terbaru dan terhebat.
Commercial systems popped up left and right, offering the latest and greatest in neural interfacing technology. There were 100 electrodes. A thousand electrodes. High bandwidth for only 99.99 a month.
Ada 100 elektroda. Ada ribuan elektroda. kecepatan tinggi 99.99 sebulan.
(Laughter)
(Tertawa)
Soon, everyone had them. And that was the key. Because, in the 2050s, if you were a neuroscientist, you could have someone come into your lab essentially from off the street. And you could have them engaged in some emotional task or social behavior or abstract reasoning, things you could never study in mice. And you could record the activity of their neurons using the interfaces that they already had. And then you could also ask them about what they were experiencing. So this link between psychology and neuroscience that you could never make in the animals, was suddenly there.
Lalu, semua orang memilikinya. Itu kuncinya. Karena pada tahun 2050an, jika Anda seorang ahli saraf, Anda bisa undang siapa pun di jalanan untuk datang ke lab. Anda bisa meneliti emosi manusia, perilaku sosial, atau penalaran abstrak, sesuatu yang Anda tak bisa pelajari pada tikus. Dan Anda bisa merekam aktivitas neuron mereka dengan menggunakan antarmuka yang telah ada. Anda juga bisa tanya mereka tentang apa yang mereka alami. Jadi hubungan antara psikologi dan ilmu saraf akhirnya dapat dipelajari pada manusia.
So perhaps the classic example of this was the discovery of the neural basis for insight. That "Aha!" moment, the moment it all comes together, it clicks. And this was discovered by two scientists in 2055, Barry and Late, who observed, in the dorsal prefrontal cortex, how in the brain of someone trying to understand an idea, how different populations of neurons would reorganize themselves -- you're looking at neural activity here in orange -- until finally their activity aligns in a way that leads to positive feedback. Right there. That is understanding.
Contoh umumnya adalah penemuan aktivitas neuron pada pemahaman. Momen "Aha", ketika semua masuk akal, cocok. Ini akan ditemukan oleh dua ilmuwan pada 2055, Barry dan Late, yang mengamati , cara otak seseorang untuk mencoba memahami sebuah ide, populasi neuron yang berbeda akan mengatur ulang dirinya-- Bagian oranye adalah aktivitas neuron lalu aktivitasnya akan menghasilkan masukan positif Di sini. Itulah pemahaman.
So finally, we were able to get at the things that make us human. And that's what really opened the way to major insights from medicine. Because, starting in the 2060s, with the ability to record the neural activity in the brains of patients with these different mental diseases, rather than defining the diseases on the basis of their symptoms, as we had at the beginning of the century, we started to define them on the basis of the actual pathology that we observed at the neural level. So for example, in the case of ADHD, we discovered that there are dozens of different diseases, all of which had been called ADHD at the start of the century, that actually had nothing to do with each other, except that they had similar symptoms. And they needed to be treated in different ways. So it was kind of incredible, in retrospect, that at the beginning of the century, we had been treating all those different diseases with the same drug, just by giving people amphetamine, basically is what we were doing. And schizophrenia and depression are the same way. So rather than prescribing drugs to people essentially at random, as we had, we learned how to predict which drugs would be most effective in which patients, and that just led to this huge improvement in outcomes.
Jadi, kita bisa tahu esensi dari manusia. Itulah yang akan menjadi solusi dari segi medis. Karena mulai tahun 2060an, dengan kemampuan merekam aktivitas neuron pada otak berbagai pasien dengan penyakit mental, daripada menentukan penyakitnya berdasarkan gejalanya, seperti yang kita alami pada awal abad ini, kita bisa menentukannya berdasarkan patologi pada tingkat neuron. Misalnya pada kasus ADHD, kami menemukan ada berbagai penyakit yang pada abad ini, semuanya disebut ADHD yang sebenarnyanya tidak saling berhubungan, kecuali terdaapat gejala yang sama. Mereka harus diobati dengan cara berbeda. Jadi cukup menakjubkan pada awal abad ini, kami mengobati berbagai penyakit itu dengan obat yang sama, hanya dengan memberi mereka amfetamin. Schizophrenia dan depresi juga demikian. Jadi daripada meresepkan obat yang sama seperti dulu, kami belajar bagaimana memprediksi obat yang paling efektif untuk pasien tertentu, dan hasilnya akan meningkat dengan pesat.
OK, I want to bring you back now to the year 2017. Some of this may sound satirical or even far fetched. And some of it is. I mean, I can't actually see into the future. I don't actually know if we're going to be drilling hundreds or thousands of microscopic holes in our heads in 30 years. But what I can tell you is that we're not going to make any progress towards understanding the human brain or human diseases until we figure out how to get at the electrical activity of neurons in healthy humans. And almost no one is working on figuring out how to do that today. That is the future of neuroscience. And I think it's time for neuroscientists to put down the mouse brain and to dedicate the thought and investment necessary to understand the human brain and human disease.
Saya ingin kita kembali ke tahun 2017. Mungkin akan terdengar seperti sindiran atau dibuat-buat. Beberapa di antaranya. Saya tak bisa lihat ke masa depan. Saya sungguh tidak tahu akankah kita mengebor ratusan atau ribuan lubang mikroskopis di kepala kita dalam 30 tahun ini. Tapi saya beritahu Anda bahwa kita tak akan mengalami kemajuan untuk dapat memahami otak manusia atau penyakitnya sampai kita menemukan cara untuk mendapatkan aktivitas listrik neuron pada manusia yang sehat. Dan saat ini, hampir tak ada yang menelitinya. Itulah masa depan ilmu saraf. Saya pikir, ini saatnya bagi ahli saraf beralih dari otak tikus lalu mendedikasikan pemikiran dan investasi yang ada untuk mempelajari otak manusia dan penyakitnya.
Thank you.
Terima kasih.
(Applause)
(Tepuk tangan)