Visit brilliant.org/scishow/ to get started learning STEM for free. The first 200 people will get 20% off their annual premium subscription and a 30-day free trial.
I enjoy your videos very much. It's wonderful to see such a young person with so much knowledge and the way your way of giving over the information is very understandable and pleasant too. Thank you. Sharing this on my Assorted and Sundry Factoid board on Pinterest and FB.
Good overall story, but: everything in that list of complications that you said they "couldn't have known" at the time of the Human Genome Project - and which you suggested could not even have been discovered until after we had the genome - were already well known when I was in grad school in the early 1990s, well before the genome project. And in fact that's why the scientific community wasn't 100% on board with the hype; there were plenty of skeptics. It was certainly an important technical achievement and has continued to impact biomedical research, but you do have that part of the story wrong.
Why do we still debate over nature and nature after maping human Genome and the human brain🧠 . We still get very prehuman pre vertebrate basic life concepts wrong. Genes don't make concepts they make proteins there is no evil Gene or violence gene or helpless adventure Gene or 🤩 Genes don't even work that way. And instincts don't exist 🤯 it's all reflexes litters physical nerve wiring . Urges witch are pressure points cravings witch are open receptors sense and yes reason and memory with are chemical imprints and learned behavior witch are clusters of neurons
Often intellectuals have hypothetical model based on philosophy they still stick philosophy why debates of nature and nature haven't improved despite study of genenome abd brain and development . Instincts in fact don't exist 🤯
@@opticalreticle Setting aside the cultural assumption that non-English speakers can't write code well: DNA is most analogous to assembly code. Can you produce any significant example of working assembly code that is basically English?
@@FurlockHolmes Assembly code is almost all English acronyms and abbreviations. If you go a level deeper to machine code, then it is just numbers not based on a specific human language.
Geneticist here! Can confirm that research benefited way more than medicine from the get go, but we get better every day at translating what we discover into useful medical applications. There's just a lot of lag time. Also can confirm that "slapping samples on the sequencer" is exactly how we get our data.
Population biologist here (who mostly does bioinformatics on vector species)... Yep. Extremely useful for research. Though a few notes. Us population biology folks were constantly telling doctors and human genetics folks that those expectations were wack. Genetics folks really should take pop bio and ideally quantitative genetics. I still routinely run into genetics folks who really don't get it. Annoyingly for me, a lot of the cutting edge techniques used for human genetics/genomics don't work as well with other species. Quite often it is due to a lack of additional data, but sometimes it is because humans have quite low genetic variability and other peculiarities. BTW: It was "fun" figuring out how to do WGS from a single mosquito back in the day. All the protocols were designed for cases where you have a lot more DNA to start with. There have been big strides since, but it still requires special methods.
Sadly we are seeing that even when sequencing supports what has been largely understood for decades, there are huge barriers to real people getting the medicines they need. And it isn't just cost. Most of it seems to be baked-in ignorance. And fear of prescribing anything other than the standard treatment - mostly for themselves and their ability to practice.
@@travcollierweirdly (but maybe understandably) a lot of STEM people don't really understand statistics and the types of influence it has on basically every aspect of every arm of science.
My impression is that you do not really understand the slightest thing. In a similar manner to you seeing a program, and poking some random addresses in memory and seeing what are the effects. Say you poke an address and the computer comes up with a blue screen and freezes. Then you go, ah, this address space has this kind of effect. No it does not. You are really clueless. You just crashed the computer, and you think the blue screen is your result. In the same way, people who run this program and for some reason had their power supplies burned out, you take their programs, diff them, and then you go, ah, those people had those specific values at those addresses, so those memory addresses are likely to cause their power supply to go poof. Obviously the reason is something else, like maybe a power surge from the electrics company, but you attribute this to a specific part of that program nonetheless. So yeah, you understand nothing, and this kind of research has no real purpose. If I am wrong, please correct me, since you are a geneticist.
The HGP's "failure" was actually its greatest achievement, IMHO. The stunned disbelief that it didn't instantly solve every mystery pushed the community to delve deeper into how gene regulation actually works and how genes interact with each other. I was studying biochemistry in college when the project was being carried out, and I was excited as everyone else. And I was as surprised as anyone else to hear that the results were nothing like what we expected. It's hard to recall just how little we understood about what we thought we were doing at the time. We had sequenced so few genomes, and so many of them were from bacteria and other single-celled organisms, that most of our expectations were based on a very skewed sample that turned out to not be even remotely representative of what goes on in mammals. We didn't know enough to know how ignorant we were. But the nature of the disconnect between our expectations and the real results was what gave us the clues to know where to look next. It told us what questions we should be asking. Sometimes, you just have to face-plant in front of a huge audience to move forward.
Do you though? Do you have to faceplant with $3B of public funding? Has anyone estimated the number of lives that could have been saved had that money gone into traditional treatment research? Or just, you know, hospitals? The lack of accountability is astonishing.
@@neildutoit5177 This kind of logic emerges on every big science project and tl;dr; is: we need big costly science projects to hit the advancing goals. Otherwise we would just stagnate: some cat somewhere in the desert is perfectly adapted to the environment and waste no extra resources. It is also just a cat, and it can't overcome some sudden challenge in the environment.
As someone currently sequencing the reference genomic map for a palm tree, I would say this project was incredibly important for my current area of study. The human genome project walked so future genetic projects could run.
I am a molecular biologist who did early work from the 80s- the early 2000s. I was isolating a copy of both the genomic sequences and a copy of the expressed mRNA one or a few a year.. I did the gene isolation, the sequencing right through to the tissue culture studies of an expressed gene's protein activity. We knew what the genomic project was likely to give us. Time. We knew it would offer us data across populations and across species to mine directly rather than spend ages getting to where we could do the protein's activity experiments. The hype was from journalists or politicians given the kind of money the project needed.
In those days and even much later, almost every single genetic paper began with a (laughable) claim that such studies would be useful for medicine. That was almost certainly to justify funding, as someone who read many of those papers I couldn't care less for the pretext, for me it was all about Prehistory.
@@arronsmith4958 And, surprisingly, as you age some cells will develop mutations that just don't do anything. Like, a muscle cell might mutate and over time it will spread throu cell division and create a 'patch' of muscle who's genome differs slightly from the rest of the body.
Its ironic that the phrase "blood related" includes the mature blood cell which does not have DNA. so the thing used to determine relation is not in red blood cells
The race for private equity to own the human genome before the HGP finished should be an Oscar-winning blockbuster several times over by now. We almost had zero access to our own genes!
it never would have been workable under patent and copyright law, the existing sequences are prior art. The main concern was and still is, the ability to patent techniques, which is what keeps stuff that is cheap to produce, like Insulin, so expensive.
From my limited experience in school ("high school"/"college" equivalent in Germany), that last sentence was the biggest understatement in history, lol! Genetics apprears endlessly complex through my small window in what we know and what we don't.
I'm kind of surprised that they have an emphasized in this video some of the larger things about DNA like how polymerase can be different and then read the DNA differently. Or that the way that The DNA is distributed between chromosomes matters except for when it doesn't. Or that the machinery that does the DNA duplication and binding is just as important as the DNA itself and alters the way it functions so if you pull the DNA out of a cell in one format without the connections for how it gets replicated it stops working and it's kind of unpredictable if you get it inserted into something with the machinery if it will work the same way because that machinery differs between organisms and duplicates itself somehow that we don't totally understand yet. Humans are actually relatively medium on the spectrum of weirdness that we found so far I would say among mammals platypi rank near the top of what the heck is going on with this machinery that manages the DNA?! I'm a programmer and a biologist that was also in college Right around the time we started having genetics as a field but just a couple years too early to actually be able to join it. I've been looking at this stuff since middle school. I apologize if some of that goes over people's heads, but what I would do is encourage you to look up DNA replication during cell division in platypi. We are not books or library, we are the campus that is housing the building complex system that they give in the metaphor. Honestly just saying that we're a complex computer program would just be easier but I know not enough people are familiar with what those look like under the hood for that metaphor to work.
@@jimmytimmy3680 I mean, all you can do is verify your hypotheses. If something works, then you changed one thing, and then it doesn't work, you've learned that that thing is important. That's one of the ways we play with stuff.
Yeah, just because the media and other external people had unrealistic expectations, it doesn't mean it was a failure. They accomplished what they set out to do, and we now have an amazing reference that will help science and medicine for generations to come.
@@wavion2absolute nonsense. The hype started at and was driven by the scientists. They made outlandish claims in order to secure $3B in funding. Money that could have been used to save thousands of lives if invested into traditional treatment research.
"It's only a failure based on the application expectations before the project started" yea next time one of my projects tanks I'm gonna tell that one to my boss and see how well she takes it. How can you people be serious? It delivers nothing it promised to deliver but oh well we just shouldn't have expected anything?
Yes, the most common diseases are more complex, but what she says at 2:55 does matter - cures for Mendelian conditions would literally be lifesavers. This hits close to home - my stepson died from Huntington's Disease just a few months ago (she did mention Huntington's in that section), and he has three children, each of whom has coin-toss odds. Praying that the researchers can figure out a solution in time for them and others in their generation.
My daughter has a genetic mutation associated with epilepsy... from 9 months old to 2.5yrs old she had 10-11 febrile seizures and 1 non-febrile seizure. Now, she is on a daily medication till she gets older. She will be 3 in October. Genetic testing is so important to science.
This video really highlights the difference between science as it is sold to the public and people who divvy up the money as opposed to the real value of science. It's often sold as having these amazing direct applications, but in reality, it is unlocking doors in a very unpredictable way.
Wow, that was fascinating! I've been clinically diagnosed with a connective tissue disease called Ehlers-Danlos Syndrome, which is... a complicated condition that comes in like 13 different varieties. It's always confused and frustrated me that they can do a genetic test to confirm if you have one specific version of EDS, but not the others, and I never understood why. But after watching this, now it makes perfect sense!
Another EDS Zebra here! I also have a congenital eye condition that was identified in my mum when she was a kid, so I've been involved in a few research projects in my time. One of those was in 2001, where the consultant said "there will be gene therapies available to you in the next 10 or 20 years". I had no expectation of that actually happening, and I was right!!!! It's part of the problem of having rare genetic conditions - our gene pool is too shallow
Same. I was checked for all known mutations, and came up negative, which landed me the more common "hypermobile EDS" diagnosis. Had to get sent to a children's hospital because that's the only geneticist in my state that was taking new patients. Mentioned that my kid has been diagnosed with autism and we're planning on seeking an EDS dx for the kid, and the Dr requested that I bring the kid to him since his current study is looking for a link between autism and EDS.
@@ThisIsATireFire I also could only access a geneticist via our national children's hospital when I first started looking for diagnosis (2007). That's brilliant that your doc is looking for that link between EDS and autism - there's a huge overlap, also with ADHD. I mentioned it to my EDS specialist last time I saw her, and she has anecdotal evidence, but nothing studied. Also, it seems impossible (or nearly so) to get an adult autism diagnosis on public health here (Ireland).
It gets really complicated. There is a whole constellation of vaguely-related "multi-systemic genetic disorders" including EDS along with Marfan Syndrome, Perrault Syndrome and so on, all affecting the skin and skeleton and connective tissues and circulatory system in various ways and degrees, and it can be hard to draw the line between them sometimes. I have what's been identified as perhaps a rare or possibly unique variety of Marfan but leaning towards EDS, with a little autism tossed in for good measure, but really, it's all guesswork.
@@slowanddeliberate6893No; compilation removes most comments and other annotations created by the programmer. Rarely are people _told_ to not add comments, it's just that good comments are cumbersome to create.
It's an oversimplification but mapping the human genome is not unlike attempting to reverse engineer a compiled driver except you don't know what the driver was controlling
After i took a genetic test, my doctors office talked to me about a medication i was taking because i have a gene that causes it to make my body process the medicine problematically, so they recommended other drugs to be. That seems helpful to me.
It swings the other way when you have a faster metabolism of certain things and they read the common doses as limits. I could respond to certain medications, but they just won't go to a higher dose.
I think they might have left out the situation where you have one condition that's caused by single point mutation so it should be very simple except every single person has a different version of the mutation when they have the disorder! That's what mine is like and because early genetics couldn't individually sequence a whole person, they just spot checked for it and surprise surprise I don't have any of the ones that were known at that time. In fact there's a good chance that if I were to get it done again using the spot check method I still wouldn't test positive for any of them because there's a darn good chance that my mother is what's called denovo which is a spontaneous mutation and here's the crazy part I might be different from my mother because once that spot mutates it tends to mutate additionally. It might not even be on a chromosome anymore, it could be a micro chromosome which would make it almost impossible to detect! On the flip side this type of mutation is what adds material for beautiful and wonderful new features to form on creatures in subsequent generations, it just kind of sucks for me because it makes my nerves a little bit wonky.
@@darcieclements4880 Thank you so much for sharing this! You've given me a bunch of new tabs for things to learn about, as well as just being a really interesting writer!! I hope your wonky nerves don't cause you much pain!
in terms of ethics concerns, all that stuff was already there, we just discriminated based on phenotype, rather than genotype. All solvable through proper regulation and once we actually do advance this stuff, there won't be any need to discriminate based on genetic conditions, because they won't exist.
You would be surprised to learn then that jokes about gnomes proliferate at NHGRI (National Human Genome Research Institute, one of the National Institutes of Health). 1000 Genomes is an older project. The current one is called, I kid you not, GnomAD.
@@clairesimpson7329 No that would not surprise me. MD for 30 years, Undergrad Biochemistry (Aka Molecular Biology in the 1980s) Lol, in 1987-1988, I did manual PCR in the undergrad Research Lab at University of Texas. Micropipettes, small culture tubes plastic 5-10 attached together in groups of 5-10, probably 1-3 ml each max. Heat bath and ice bath with a kitchen timer, lol. IIRC we used Taq DNA Polymerase, but it was a long time ago. Every Professional occupation has their own specialized language with bizarre (to outsiders) abbreviations and lingo. With often dark humor associated with it. The Military has thousands so does science. Medicine also. It is a coping mechanism with high stress jobs. My ex wife is also a MD and we had to be careful with conversations over dinner with others outside Medicine. The Surgeons were often the worst, lol, when the patient was under anesthesia. I remember many of those. As a Medical Student, I just kept my mouth shut, I knew many of these conversations were not acceptable, but context and human behavior under stress is simple reality.
@@shainazion4073 They did something with genes in Europe like in 2003 or so buti haven't heard much since. Josh had a Bone Marrow Transplant in 1985 but he didn't engraft. He did live till 2002 thankfully.
Science communication doesn't need click-bait titles. To be fair, you can sequence your personal genome and store them in a small pen drive in your wallet in 2016 and now. I'm a geneticist and I have worked with terabytes of sequencing data to know that this is feasible.
Sci-show editors: Please do not interrupt your presenters mid-sentence for a sponsorship ad. You did not have to choose that point to make the cut and transition, it comes across as disrespectful of the speaker and is disruptive and annoying. /rant
@@calvindevries For a bunch of smart people it's curious you don't look for a solution like Sponsor Block and instead shout into the void that is the UA-cam comment section.
As a software engineer looking back on this, it seems obvious in hindsight. If each IF block I made only had a 30% chance of working, of course that control logic would dominate the business logic.
A genetic study, for patients lucky enough to get one (they're expensive) can go a long way in determining what specific pharmaceuticals are appropriate to treat mental health conditions.
I feel like the video undersold the potential of genetically targeted medicine. If I hadn't known about "these genes work better with that medication", I don't think I would have learned it from this video, and I definitely wouldn't have realised that it had more potential than just gene therapy.
A medication for my kid went badly wrong and nearly killed him. We knew immediately that the med caused it, but not why. We were referred to a genetic screening that found he has a mutation in an enzyme responsible for breaking down a category of medicines (including that one). This changed the breakdown speed and meant a slow-release dose will OD him 10 hours later. He's in that list of rare side effects meds always warn about. Because of genetics we know to avoid several medicines with him, not just the one. General genetic screening would have avoided this, but it's too expensive. Makes me wonder how much the promise of gene mapping wasn't realized because of money, not science.
And frequently, if drs know what section the suspected mutation is in, they won't request sequencing the whole genome, just that section that they specialize in. Rather frustrating when there's multiple health issues and having the whole thing would be helpful. Also incredibly expensive at 2k US per round.
10:53 To clarify for viewers who arent familiar with DNA sequencers: That is an Illumina MiSeq, it is not even remotely capable of sequencing a single human genome. For that, you're better off using an Illumina NovaSeq, or if you want something cheaper and low-throughput you could go with an Element AVITI. The MiSeq is better suited for sequencing MUCH smaller fragments of our genome, such as a specific list of genes linked to congenital health conditions. In fact, that's exactly where DNA sequencing shines in the healthcare field. A cheaper panel of testing to *contribute* diagnoses of health conditions that healthcare providers would otherwise be unable to identify. You can even do it with whole-genome sequencing in more urgent cases as a valuable asset in finding a diagnosis. This video gives the impression that DNA sequencing for healthcare isn't all that helpful, when in reality it is an incredibly important tool in the toolbox of modern medicine. It's not the only tool, but a revolutionary diagnostic tool, not unlike MRI's or X-rays.
There's also several (minimum) days worth of prep before that "wack a sample down" on the sequencer step. (My 96-well 'new to my core lab' protocol RNA extractions were not great today. So a days labor and a couple grand in reagents/consumables in the haz waste bottle. Tomorrow will be better.)
@laurakemp5979 To be fair, it's better to fail at extractions than to fail at library prep or sequencing, but it's still a whole-shift process more often than not
//this bit doesn't seem to do anything but everything breaks if you take it out Is a comment I've definitely seen more than once. Maybe computer code and DNA aren't so different.
Yeah there's some of us that specialize in dealing with code that didn't get nice little helpful notes and people need it reverse engineered. One of my first jobs was reverse engineering something that was written by a guy who literally was hit by a bus and died suddenly so that it could be documented for long-term maintenance. What I learned on that job was to always make sure everything I produced was well documented in case that happened to me because you don't want to leave your coworkers in that situation.
@@LikelyToBeEatenByAGrueoh yeah I love that, I do prefer and always ask people to put in the specifics of what happens if you remove it even if they can't figure out what the thing does that way if I come across it and I realize what it's actually doing I can update it and same for anyone else who comes across it. Just because you don't know why the piece of code is required doesn't mean somebody else won't have the experience necessary to realize oh yes this is actually doing XY and z thus it needs to be left in. And occasionally you might be able to see that and be like oh it's because this is multithreaded and it should have been single threaded let me fix that fundamentally.
Only when the person making it isn't thorough...or is looking for "job security" by being the only one who can maintain their code. Unfortunately, that can work, and being meticulous (and/or including tutorials in your programs and teaching others how to use them) isn't necessarily rewarded.
There were cheaper, simpler and more holistic things that could of been done instead... But were ignored... Things that may have actually worked wonder for human medicine but no one can make huge profits on it so they were never even looked at, if not downright ignored... As always ..
@@peterzotti6430 And I am a victim, get out of here, I would not be alive and even if I was, I would not be able to type this message, if not for the amazing effort of doctors and researchers all over the world
The biggest and most important thing was finding out WHY certain health issues are passed along. Most people who have celiacs for instance have 2 specific genes in common. But that only is important if those genes get triggered for some reason. But now the trigger has to be found. We also learned about epigenetics, the switches that do things to genes. That are sometimes inherited.
@@topogigio7031 I'm literally criticizing the for profit medical industrial complex and you're accusing me of being a snake oil sales man... Make it make sense...
Not a failure at all. We simply learned that genetic expression functions much more complexly than we initially assumed, therefore it is taking longer to understand the implications of everything and develop actionable therapies based on the results. I don't think it will really kick off until we have AIs that can continuously simulate genetic expression on digital human models. That will go so much faster than the status quo, where we can only test one condition at a time in organized lab studies that take years to complete. There is also the ongoing ethical question of to what extent we should genetically modify ourselves, which is still unresolved.
No, it is a failure in its own terms. We learned that the central assumption behind the genome project is wrong. You are not defined by your genome. Your mother's life before your conception and indeed your father's life before your conception and your life history in the womb and afterwards are much more important than assumed. We are not mere vessels for our genes, as Dawkins claimed. Epigenetics has destroyed this claim. People who have cloned their pets have discovered this first hand. The clones are different, often very different from each other. People do not have blueprints. It's more like a cake. If you follow a recipe twice you will end up with similar cakes but never identical ones. If you cook one a bit longer or mix one a bit differently it could be tasty or burned. Even that analogy isn't quite right because organisms actually edit their own genomes, they leverage darwinian evolution, for instance our immune system deliberately "evolves" antibodies when we get infected. And this is without mentioning the trillions of other organisms that our bodies are hosts to, all with their own genomes, immune systems etc. AI, no matter how powerful, will never be able to simulate that, it is a chaotic system.
Modifying yourself isn't an ethical question, modifying your neighbor is! 😊 (you used the general ourself as humans, I understood. Extra context incoming. Our genes are modified without recognition or choice by external factors - having a choice is not a morality question, it's a functional one. The options of choice and methods to choose would be an ethical one.)
@@hayuseen6683 I was referring primarily to the scenario of genetic modification for infants. Infants cannot provide consent to genetic modification for obvious reasons, and while most people would agree that genetic treatment to prevent specific genetic diseases would be ethical, going beyond that to other modifications would cause significant controversy. Adults are able to choose to do genetic modification, but the ethical problem then becomes fairness of availability. Wealthy individuals will have much more access to genetic healthcare (or in the future, possibly even physical, cosmetic, or cognitive enhancements) and this can become another form of class-based inequality.
@@Outshinedsg I figured, though "extent" seems to imply how much, not who gets to do it to who. Some people care about extent - making us less 'human' via transhumanism.
The library metaphore is nice. There are also books in the library about maintaining the library, books about bookbinding, and books that contain instruction on how to arrange the books, scribblings on the walls with bug fixes, etc.
Ray Kurzweil talks about the human genome project in his book "The Singularity is Near". He noted: 1. At the start of the project in the early '90s, critics said that the project would take over 100 years. Kurzweil noted that estimate was correct using the existing technology. 2. The project planned and developed new technologies as it ran. These tecnolgies drastically improved DNA scanning, which reduced the project's time. 3. The project finished early (two or three years ahead of schedule), and below budget. In its wake, the human genome project left a set of technologies that allowed for rapid and cost effective analysis of DNA from humans and other animals. This pushes scientific research. I assume this also helped with the quick analysis of the SARS Covid-19 virus. Please correct me if I have this wrong.
It’s probably a good thing that it was hyped up like it was, or it wouldn’t have been funded. Framing it as a “big experiment that won’t directly impact patients right away, but help technology evolve. But we don’t know how yet” wouldn’t have gotten peoples attention, or captured their imaginations.
But it was helpful to figure out some things. For example, by looking at a part of code they verified that I have hemochromatosis. Which doesn't need to be rewritten. It just means that I have to donate blood in order to survive. I also love the part about "junk" in the DNA. Because everything in this world works differently than we would think they should. Nothing is as simple as we would love to believe.
tl:dr It failed in the sense that it over-promised and under-delivered. But succeeded in giving us an understanding of just how bloody complex the genome actually is. And we can do more stuff now.
@@cedriceveleigh Then this comment wasn't for you. I enjoyed the video actually. The comment was for the courtesy of all of those who are likely to scream "CLICKBAIT"... cause it isn't clickbait.
@jliller that's a bit of a miscalculation too. Without trying again, one cannot be certain a failure is a failure. The confluence of failure is knowledge is more accurate to my point, implying that whomever uses it (individuals or even concepts like science) does learn from it.
"Failure" is a loaded word to use with anything scientific. Like, sure, use it with investors when they were expecting certain technologies/results. But in a scientific sense? The entire point is to develop a hypothesis, test it and see what happens. There is no "failed" outcome. You learn something new either way and broaden your understanding. Either, yes, it works as you think it did and you build off of it. Or, no, it doesn't work like you thought and suddenly you have a ton of new possibilities to consider. There's no "bad" outcome here.
@@Tfin Umm... I'm still not sold on that one. Maybe it's the possibility of them making an honest error - or maybe more that if it's deliberate, then it's quite tasteless and disrespectful
I think most scientists knew in advance that there was a lot of work beyond knowing the sequence that would need to be done in order to understand the overall physiology.
DNA seems to work a lot like a ROM of a video game. There are functional bits and data bits. And only by understanding the decoder can you follow the code and figure out which is which.
Another major problem was the protein folding project. In order to understand the machines those sequences represent, you have to fold the proteins to see what the machines do. This is many, many orders of magnitude more difficult than finding the sequences. The human genome protein folding project will eventually complete due to the exponential increase of computational power of both hardware and software as a function of time. P,S. I have many powerful GPUs and occasionally lend them to internet projects such as protein folding for the Covid 19 virus when that was necessary.
This is when you slipped into a straw man argument: 10:11 - no one said "easy cures to everything." They were right that sequencing the genome has opened up new therapies, and tests for diseases. They weren't exaggerating. It's only been 25 years or so.
actually a lot of bad science journalists took comments like we may be able to provide gene therapy cures for some specific monogenetic diseases, and spun them into comments saying that it would be trivial to fix every disease with gene therapy within a few years. lots of other journalists told equally big whoppers about other aspects of the program as well. most scientists in the field had more sense.
I don't like calling something not meeting the expectations of people who made stuff up about it on their own a failure when it accomplished its actual stated goal of sequencing the whole genome perfectly
I had my full genome sequenced for a few hundred dollars in 2019. Not quite on the level of “genome in the wallet,” but it’s still pretty incredible when you consider the effort and expense it took to do the first time.
It's frustrating that this video spent the first 12 minutes in the terrible framing of "things are only successful if they lead to immediate clinical benefits" and then crammed in the correct take that "the human genome is necessary to even *start* understanding human biology and that *will* ultimately lead to clinical benefits" at the end. People aren't going to remember the caveat.
I know the title is meant to get people to click - but so many people only read titles. As a genomics PhD, the title offends me, and it is a disservice to many people who devote their lives every day to studying the genome. I get it, you need people to click on the video and engage; I guess the title accomplishes the goal - but at what cost?
Agreed. Video filled with misinformation too, not sure they've ever heard of the impact genome-wide association studies, polygenic risk scores, Mendelian randomisation, have actually had on revolutionising modern medicine and couldn't exist without the human genome project. This feels like poorly researched tabloid journalism
I posted a similar rant before reading your comment. Fellow Geneticist here and I completely agree. In a world that is getting increasingly mistrusting of science, popular science communication channels can do better than click baits
while i agree the click bait tile was bad, i don't think it is fair to criticise the presenter for only doing twice as good as mainstream media with massively more resources. yes it could have been better, but this is social media, so you have to make sure your expectations are low enough.
@@grokitall science and facts can't change just because it is social media. I thoroughly appreciate the presenter breaking down hard scientific topics and presenting them to a wider audience. Which is exactly why I'm upset at the needless click bait that can contribute to miscommunication.
@@grokitall Yeah, no. That might fly on Facebook. It does not fly on UA-cam. This site is as much a knowledge resource as it is social media. There are plenty of excellent, well researched videos on UA-cam about this sort of thing. Complaining about it is perfectly valid.
I'm pretty sure there are some of my cells on the cards I carry around, so technically there is my entire genome on a card in my pocket. Let's ignore that it'd be there without the human genome project.
Gotta love Savannah, so much enthusiasm and humor, without expense on the science :) Reminder of the best humanity has to offer in these uber-stressful times :) Many thanks, much obliged :) :) :) :) :)
As always, I love Savannahs delivery. The humour they inject into the material makes it much more engaging. Keep up the good work, and remember to take your breaks.
in alot of irony this video made the exact mistakes that the earlier scientists made when talking about what the genome actually does! the genome is NOT a _blueprint_ of a human, its more like a recipe for one (without the picture preview). the difference here is that a blueprint has an end result to be attained but a recipe does not, its just a list of ingredient (the proteins) and instructions ('junk DNA'). on top of that many of the instructions are basically like compiled code, a giant self referential mess of instructions that if followed exactly will make a human but small mistakes can potentially alter later instructions in enormous unpredictable ways. this is why its been so hard to figure it out, and also why a few diseases where easy; those where part of the ~20K orso proteins ingredient that we can easily see and not the instruction list.
I get what you are saying, but I'm not sure that analogy holds - if I'm not mistaken, recipes typically have an end-result to be attained, or have I been cooking wrong this whole time? 😄
@@caydennormanton9682 yes you have an end result because you have a preview of that, your cells dont have an end result to work towards. that was my whole point
@@sudazima ...and my point is that you don't need a picture to have an end-result, the end-result is just the result at the end of a process, regardless of what was used to make it. But, alas, my comment was in jest, and I understood your meaning anyway 🙂
@@caydennormanton9682Most people's cannot even properly cook a perfect recipe while having knowledge of how the result should be. Now imagine compiled materials on top of that. I know you got the point already before, just want to say how insane it is our body is even to produce it properly. I for sure wouldn't want to be 'chef' actively having to manage my own 😅
Even when I first heard of the genome project, I knew it was just a first step. If I might make my own analogy, it's like when we first mapped the Earth by satellite. That map helped us out a lot in understanding the Earth but it couldn't tell us where all the diamonds were. There is a lot we still won't know until we actually get there.
Hell, even the end of Metal Gear Solid (a game from 1998) kind of goes against the overhyping by people at the time in regards to the Human Genome Project, in a part of Naomi Hunter's monologue at the end of game. "Each person is born with their fate written into their own genetic code... it's unchangeable, immutable... But that's not all there is to life. I finally realized that. I told you before. The reason that I was interested in genes and DNA. Because I wanted to know who I was... where I came from. I thought that if I analyzed my DNA I could find out who I was, who my parents were. And I thought that if I knew that, then I'd know what path I should take in life. But I was wrong. I didn't find anything. I didn't learn anything. Just like with the Genome Soldiers... you can input all the genetic information, but that doesn't make them into the strongest soldiers. The most we can say about DNA is that it governs a person's potential strengths... potential destiny. You mustn't allow yourself to be chained to fate... to be ruled by your genes. Humans can choose the type of life they want to live."
I was playing this as background noise while I worked on some hobby stuff, but 8 mins into the vid, I’m asking chatgpt for clarifications of dna, mrna, genome, etc, going into depths of this subject I never was interested in. Good job!
Back when i was 17, and studying A-Level Biology, we were told that only when a cell was preparing to divide did the chromasomes form into the familiar X-shaped pairs. Most of the time, they were loosely packed into the nucleus of the cell... and that was all we were told. Forty odd years later, I finally learned why our genes spend most of their time loosely coiled in the nucleus, tonight. It's so the DNA can be read more easily by the cells transcription machinery! Of course, this may not have been known back then, a case of 'we know what it does', but not 'why'. This situation is common right across all scientific fields, as we make leaps in both understanding and technology.
It was known a lot more than 40 years ago. People picture chromosomes all doubled and packed up with histones and other stuff in that stage of mitosis because that image is the one where they are most visible in a stained slide under a light microscope. Most of the time they are unravelled, accessible to replication, transcription and repair mechanisms, as well as factors which block some sequences, or how could they work? That's why they are only visible in mitosis, when they will have to migrate to the two halves of the dividing cell without getting tangled or mis-sorted.
it seems considering its sequel project encode is still ongoing that is not much of a failure and more a thing of "it turns out its much more complicated and nuissanced than we though, what we have is mostly useless... because we don't understand it yet"
"To map the very stuff of life; to look into the genetic mirror and watch a million generations march past. That, friends, is both our curse and our proudest achievement. For it is in reaching to our beginnings that we begin to learn who we truly are." -Academician Prokhor Zakharov, "Address to the Faculty"
"We hold life to be sacred, but we also know the foundation of life consists of a stream of codes not so different from the successive frames of a watchvid. Why then cannot we cut one code short here, and start another there? Is life so fragile that it can withstand no tampering? Does the sacred brook no improvement?" ~ Chairman Sheng-ji Yang, "Dynamics of Mind"
"The genetic code does not, and cannot, specify the nature and position of every capillary in the body or every neuron in the brain. What it {can} do is describe the underlying fractal pattern which creates them." - Academician Prokhtor Zakharov, Nonlinear Genetics
I have a sort of metaphor for this. It's like a computer wrote it's own program in assembly code without human readability in mind. The situation is kinda similar to PvZ modding in a hex editor. We kinda just have to guess what each bit does, and write down how it effects the game when changed. Maybe someday we can learn how to "program" a genome, that would be interesting.
My friend has sons and brothers with Partington's syndrome, a disorder directly linked to a specific gene mutation on the Y chromosome. However, each son and brother is a unique person with variations in cognitive, muscular, and speech (etc.) difficulties associated with the mutation. They also have a broad spectrum of personalities, and it is clear how environmental factors have affected them, such as different parenting styles and choices in educational resources. My point here is even knowing the exact mutation on a gene doesn't tell the whole story of a person. I am so glad we are still studying, still learning and still caring about all of it.
I clicked on this video misreading the title as the human gnome project. Kind of disappointed there wasn't some secret project to make us more gnome like.
I think it's worth mentioning that like. as far as i know, as of right now, even one-gene-zebra conditions like *mine* can't really just like. be edited in a living organism like those promises implied. like you can't just graft a working copy of a gene into a patient who didn't start with one, even if you know exactly which gene is causing the problem.
A few such conditions have therapies now by removing some cells, patching a good copy of the gene into them using a viral vector and returning the cells to the patient. Mostly it's been done for quite rare conditions, but recently two gene therapies for sickle cell anemia have become available. One patches in genes for normal hemoglobin, while the other reactivates the production of fetal hemoglobin. While these therapies are expensive, they may be less expensive than repeatedly treating e.g. sickle cell crises. I hope something will be developed for your condition. Keep up with the research and there might be a clinical trial you can join.
The bit about all metaphors being somewhat fictional is super important. One of the coolest assignments I had in grad school was talking about the potential misunderstandings and misconceptions that come from calling CRISPR a "gene editing" tool
Excellent summary. Me, Molecular Biology undergrad (it was called Biochemistry degree in the 1980s), to Med School, 30 years as a MD, PCP, Family Medicine. The Human Genome Project was the easiest. The "low hanging fruit". Never lost my fascination with Molecular Biology and tried to keep up with advances over time. Sequencing the Genome was very scalable and with computerization and technology advancing was completed quicker than predicted. LOL, I actually did manual PCR as an undergrad, Micropipettes and small culture tubes, heat baths and ice baths using repurposed manual kitchen timers. Took Molecular Biology in my 2nd year at MIT, taught by Harvey Lodesh, from Preprints of the 1st edition of Molecular Cell Biology, he sent all the students a signed first edition, kept his promise, I still own it. Dr Lodesh is still working, a great teacher and a great human, would talk to him after class many times. A true research scientist and a Great teacher, unfortunately not that common anymore, publish or perish right? The Human Genome Project was the easy part and was definitely overhyped. But it was a start and had to be done and paid for. Now the really hard work began, proteomics, regulation of gene expression in different tissues, in health and in disease states, RNomics, etc. It will take a long time to figure this out. Humanity has scratched the surface, but the really hard work is not "low hanging fruit" we are beyond that. Great vid!
Big scientific and engineering projects present huge up sides for over-promising and scant down sides. So not seeing big surprises here. The details are fascinating nonetheless.
most pure science projects return 7 times more money than was spent on them as direct benefits, and often a lot more with indirect benefits, you just don't know where the gains will come from. this is why you promise benefits, but are light on specifics and you make sure not to over promise on specifics.
Ironically, some of the tools we got out of the HGP were sequences of non-human organisms, like E.coli and fruit flies, the idea being to develop techniques in simpler genomes before progressing to more complex genomes (us; we are the more complex genome). Sequencing those other organisms has also contributed to medical advancements because there are just some things we'll never be able to study in humans (like the genetics of development).
Visit brilliant.org/scishow/ to get started learning STEM for free. The first 200 people will get 20% off their annual premium subscription and a 30-day free trial.
I enjoy your videos very much. It's wonderful to see such a young person with so much knowledge and the way your way of giving over the information is very understandable and pleasant too. Thank you. Sharing this on my Assorted and Sundry Factoid board on Pinterest and FB.
Good overall story, but: everything in that list of complications that you said they "couldn't have known" at the time of the Human Genome Project - and which you suggested could not even have been discovered until after we had the genome - were already well known when I was in grad school in the early 1990s, well before the genome project. And in fact that's why the scientific community wasn't 100% on board with the hype; there were plenty of skeptics. It was certainly an important technical achievement and has continued to impact biomedical research, but you do have that part of the story wrong.
What's up with the click bait title? shame.
Why do we still debate over nature and nature after maping human Genome and the human brain🧠
. We still get very prehuman pre vertebrate basic life concepts wrong. Genes don't make concepts they make proteins there is no evil Gene or violence gene or helpless adventure Gene or 🤩
Genes don't even work that way.
And instincts don't exist 🤯 it's all reflexes litters physical nerve wiring .
Urges witch are pressure points cravings witch are open receptors sense and yes reason and memory with are chemical imprints and learned behavior witch are clusters of neurons
Often intellectuals have hypothetical model based on philosophy they still stick philosophy why debates of nature and nature haven't improved despite study of genenome abd brain and development .
Instincts in fact don't exist 🤯
"Unlike computer code, the genetic code doesn't contain helpful annotations."
Computer programmers: *Sweat nervously*
well written computer code is basically english
I heard that and thought "Savannah, I have some bad news for you."
But it's also worth noting that one can get better code by avoiding commenting.
@@opticalreticle Setting aside the cultural assumption that non-English speakers can't write code well:
DNA is most analogous to assembly code.
Can you produce any significant example of working assembly code that is basically English?
@@FurlockHolmes Assembly code is almost all English acronyms and abbreviations.
If you go a level deeper to machine code, then it is just numbers not based on a specific human language.
Geneticist here! Can confirm that research benefited way more than medicine from the get go, but we get better every day at translating what we discover into useful medical applications. There's just a lot of lag time. Also can confirm that "slapping samples on the sequencer" is exactly how we get our data.
Population biologist here (who mostly does bioinformatics on vector species)...
Yep. Extremely useful for research. Though a few notes.
Us population biology folks were constantly telling doctors and human genetics folks that those expectations were wack. Genetics folks really should take pop bio and ideally quantitative genetics. I still routinely run into genetics folks who really don't get it.
Annoyingly for me, a lot of the cutting edge techniques used for human genetics/genomics don't work as well with other species. Quite often it is due to a lack of additional data, but sometimes it is because humans have quite low genetic variability and other peculiarities.
BTW: It was "fun" figuring out how to do WGS from a single mosquito back in the day. All the protocols were designed for cases where you have a lot more DNA to start with. There have been big strides since, but it still requires special methods.
Sadly we are seeing that even when sequencing supports what has been largely understood for decades, there are huge barriers to real people getting the medicines they need.
And it isn't just cost.
Most of it seems to be baked-in ignorance. And fear of prescribing anything other than the standard treatment - mostly for themselves and their ability to practice.
@@travcollierweirdly (but maybe understandably) a lot of STEM people don't really understand statistics and the types of influence it has on basically every aspect of every arm of science.
@@polyvgI want to know more about this
My impression is that you do not really understand the slightest thing. In a similar manner to you seeing a program, and poking some random addresses in memory and seeing what are the effects. Say you poke an address and the computer comes up with a blue screen and freezes. Then you go, ah, this address space has this kind of effect. No it does not. You are really clueless. You just crashed the computer, and you think the blue screen is your result. In the same way, people who run this program and for some reason had their power supplies burned out, you take their programs, diff them, and then you go, ah, those people had those specific values at those addresses, so those memory addresses are likely to cause their power supply to go poof. Obviously the reason is something else, like maybe a power surge from the electrics company, but you attribute this to a specific part of that program nonetheless. So yeah, you understand nothing, and this kind of research has no real purpose. If I am wrong, please correct me, since you are a geneticist.
The HGP's "failure" was actually its greatest achievement, IMHO. The stunned disbelief that it didn't instantly solve every mystery pushed the community to delve deeper into how gene regulation actually works and how genes interact with each other. I was studying biochemistry in college when the project was being carried out, and I was excited as everyone else. And I was as surprised as anyone else to hear that the results were nothing like what we expected. It's hard to recall just how little we understood about what we thought we were doing at the time. We had sequenced so few genomes, and so many of them were from bacteria and other single-celled organisms, that most of our expectations were based on a very skewed sample that turned out to not be even remotely representative of what goes on in mammals. We didn't know enough to know how ignorant we were. But the nature of the disconnect between our expectations and the real results was what gave us the clues to know where to look next. It told us what questions we should be asking.
Sometimes, you just have to face-plant in front of a huge audience to move forward.
Such an interesting perspective
So you're saying that our scientists were so preoccupied with whether they could, they didn't stop to think if they should.
Almost like it proved that evolution was random nonsense that just happened to not be fatal before reproduction.
Do you though? Do you have to faceplant with $3B of public funding? Has anyone estimated the number of lives that could have been saved had that money gone into traditional treatment research? Or just, you know, hospitals? The lack of accountability is astonishing.
@@neildutoit5177 This kind of logic emerges on every big science project and tl;dr; is: we need big costly science projects to hit the advancing goals. Otherwise we would just stagnate: some cat somewhere in the desert is perfectly adapted to the environment and waste no extra resources. It is also just a cat, and it can't overcome some sudden challenge in the environment.
As someone currently sequencing the reference genomic map for a palm tree, I would say this project was incredibly important for my current area of study. The human genome project walked so future genetic projects could run.
Wouldn't have to run, could crawl, slither or swim 🤷♂️😂
Which variety of Palm are you researching now ?
And we were LUCKY that private equity firms didn’t win the race, making the entire human genome privately owned!
@@avwholesomegamer Genes are being patented. They're already there.
@@mocast0974 you mean the SCN1A? Yeah, that was facepalming, at least for me. What humanity had became...
I am a molecular biologist who did early work from the 80s- the early 2000s. I was isolating a copy of both the genomic sequences and a copy of the expressed mRNA one or a few a year.. I did the gene isolation, the sequencing right through to the tissue culture studies of an expressed gene's protein activity. We knew what the genomic project was likely to give us. Time. We knew it would offer us data across populations and across species to mine directly rather than spend ages getting to where we could do the protein's activity experiments. The hype was from journalists or politicians given the kind of money the project needed.
In those days and even much later, almost every single genetic paper began with a (laughable) claim that such studies would be useful for medicine. That was almost certainly to justify funding, as someone who read many of those papers I couldn't care less for the pretext, for me it was all about Prehistory.
I carry my genome around in most of the cells of my body
Underrated comment
Dido
My RBC's are being problematic there... but same!
@@arronsmith4958 And, surprisingly, as you age some cells will develop mutations that just don't do anything. Like, a muscle cell might mutate and over time it will spread throu cell division and create a 'patch' of muscle who's genome differs slightly from the rest of the body.
Its ironic that the phrase "blood related" includes the mature blood cell which does not have DNA. so the thing used to determine relation is not in red blood cells
The race for private equity to own the human genome before the HGP finished should be an Oscar-winning blockbuster several times over by now. We almost had zero access to our own genes!
Insane. Absolutely, utterly insane.
Woah that was evil
@@XiELEd4377 So pretty typical for big corporations :D
@@MySerpentine
Patenting of gene by companies have become - look up SCN1A
it never would have been workable under patent and copyright law, the existing sequences are prior art. The main concern was and still is, the ability to patent techniques, which is what keeps stuff that is cheap to produce, like Insulin, so expensive.
"It's more complicated than what we thought it would be."
"It always is..."
@@TheDredConspiracy I was hoping for something, not sure what I was going to get...
From my limited experience in school ("high school"/"college" equivalent in Germany), that last sentence was the biggest understatement in history, lol! Genetics apprears endlessly complex through my small window in what we know and what we don't.
Epigenetics, who knew.
I'm kind of surprised that they have an emphasized in this video some of the larger things about DNA like how polymerase can be different and then read the DNA differently. Or that the way that The DNA is distributed between chromosomes matters except for when it doesn't. Or that the machinery that does the DNA duplication and binding is just as important as the DNA itself and alters the way it functions so if you pull the DNA out of a cell in one format without the connections for how it gets replicated it stops working and it's kind of unpredictable if you get it inserted into something with the machinery if it will work the same way because that machinery differs between organisms and duplicates itself somehow that we don't totally understand yet. Humans are actually relatively medium on the spectrum of weirdness that we found so far I would say among mammals platypi rank near the top of what the heck is going on with this machinery that manages the DNA?! I'm a programmer and a biologist that was also in college Right around the time we started having genetics as a field but just a couple years too early to actually be able to join it. I've been looking at this stuff since middle school. I apologize if some of that goes over people's heads, but what I would do is encourage you to look up DNA replication during cell division in platypi. We are not books or library, we are the campus that is housing the building complex system that they give in the metaphor. Honestly just saying that we're a complex computer program would just be easier but I know not enough people are familiar with what those look like under the hood for that metaphor to work.
"So stuff is more complex that we initially thought?"
"Always has been."
turns out the real genome was inside of us all along
I think the real genome is also in the friends we made along the way.
Like Prince Albert in a can? 😂. Ok, I’m dating myself 🎉😂😂
*angry upvote*
@@neildutoit5177 like the bacteria that we carry around...or that carries us around
@@thesjkexperienceif you don't stop dating yourself, you'll grow hair on your palms and go blind.
I love that the pitch was to keep a copy of your genes in your jeans.
There was a ginuwine song about that.
Despite all of my genes, I'm still a rat in some jeans.
@@Crosshair1990Despite all my genes I am still just some genes in some jeans.
I keep my gene-copier in my jeans already (unless you ask politely)
Squids got genes! Squids got genes! Squids got genes!
“ Task failed successfully “, is absolutely correct. I loved this video! Tysm
You learn more from mistakes than from success.
@@jimmytimmy3680 amen to that!!!
@@jimmytimmy3680 I mean, all you can do is verify your hypotheses. If something works, then you changed one thing, and then it doesn't work, you've learned that that thing is important. That's one of the ways we play with stuff.
It's only a failure based on the application expectations before the project started. We had to get the map. It's a work in progress.
Plus CRISPR
The idea of genetic specific treatments are still in the works as you say. HGP is the infrastructure.
But this channel needs clickbait crap headlines for views, so...
Yeah, just because the media and other external people had unrealistic expectations, it doesn't mean it was a failure. They accomplished what they set out to do, and we now have an amazing reference that will help science and medicine for generations to come.
@@wavion2absolute nonsense. The hype started at and was driven by the scientists. They made outlandish claims in order to secure $3B in funding. Money that could have been used to save thousands of lives if invested into traditional treatment research.
"It's only a failure based on the application expectations before the project started" yea next time one of my projects tanks I'm gonna tell that one to my boss and see how well she takes it. How can you people be serious? It delivers nothing it promised to deliver but oh well we just shouldn't have expected anything?
Yes, the most common diseases are more complex, but what she says at 2:55 does matter - cures for Mendelian conditions would literally be lifesavers. This hits close to home - my stepson died from Huntington's Disease just a few months ago (she did mention Huntington's in that section), and he has three children, each of whom has coin-toss odds. Praying that the researchers can figure out a solution in time for them and others in their generation.
Yes!!
Really surprised they didn't mention Cystic Fibrosis, the genetic disease that spurred a lot of the HGP research on
I pray too!
My daughter has a genetic mutation associated with epilepsy... from 9 months old to 2.5yrs old she had 10-11 febrile seizures and 1 non-febrile seizure. Now, she is on a daily medication till she gets older. She will be 3 in October.
Genetic testing is so important to science.
This video really highlights the difference between science as it is sold to the public and people who divvy up the money as opposed to the real value of science. It's often sold as having these amazing direct applications, but in reality, it is unlocking doors in a very unpredictable way.
Wow, that was fascinating! I've been clinically diagnosed with a connective tissue disease called Ehlers-Danlos Syndrome, which is... a complicated condition that comes in like 13 different varieties. It's always confused and frustrated me that they can do a genetic test to confirm if you have one specific version of EDS, but not the others, and I never understood why. But after watching this, now it makes perfect sense!
Me, too! And (pure coincidence) my partner.
Another EDS Zebra here! I also have a congenital eye condition that was identified in my mum when she was a kid, so I've been involved in a few research projects in my time. One of those was in 2001, where the consultant said "there will be gene therapies available to you in the next 10 or 20 years". I had no expectation of that actually happening, and I was right!!!! It's part of the problem of having rare genetic conditions - our gene pool is too shallow
Same. I was checked for all known mutations, and came up negative, which landed me the more common "hypermobile EDS" diagnosis.
Had to get sent to a children's hospital because that's the only geneticist in my state that was taking new patients. Mentioned that my kid has been diagnosed with autism and we're planning on seeking an EDS dx for the kid, and the Dr requested that I bring the kid to him since his current study is looking for a link between autism and EDS.
@@ThisIsATireFire I also could only access a geneticist via our national children's hospital when I first started looking for diagnosis (2007). That's brilliant that your doc is looking for that link between EDS and autism - there's a huge overlap, also with ADHD. I mentioned it to my EDS specialist last time I saw her, and she has anecdotal evidence, but nothing studied. Also, it seems impossible (or nearly so) to get an adult autism diagnosis on public health here (Ireland).
It gets really complicated. There is a whole constellation of vaguely-related "multi-systemic genetic disorders" including EDS along with Marfan Syndrome, Perrault Syndrome and so on, all affecting the skin and skeleton and connective tissues and circulatory system in various ways and degrees, and it can be hard to draw the line between them sometimes. I have what's been identified as perhaps a rare or possibly unique variety of Marfan but leaning towards EDS, with a little autism tossed in for good measure, but really, it's all guesswork.
4:20 "Unlike a computer code, genes does not contain helpful annotations..."
As a programmer, well.. 💀
Do they tell you not to annotate to make reverse engineering by decompiling harder?
@@slowanddeliberate6893No; compilation removes most comments and other annotations created by the programmer. Rarely are people _told_ to not add comments, it's just that good comments are cumbersome to create.
@@DJBarry777 Okay. Thanks for letting me know.
It's an oversimplification but mapping the human genome is not unlike attempting to reverse engineer a compiled driver except you don't know what the driver was controlling
@@slowanddeliberate6893 to add on top imagine you are doing calculations and you have to write to explain each step or you could just do it directly
I worked on that a bit as an undergrad! Strangely my landlord’s name at the time: Gene Poole. true story
Quite an arousing name for sure. Must be daunting for its bearer tho.
Never let it be said that God our Father has no sense of humor...classic dad joke. 😆
After i took a genetic test, my doctors office talked to me about a medication i was taking because i have a gene that causes it to make my body process the medicine problematically, so they recommended other drugs to be. That seems helpful to me.
It swings the other way when you have a faster metabolism of certain things and they read the common doses as limits. I could respond to certain medications, but they just won't go to a higher dose.
A library that was never meant to be a library, that just developed into one over time made from the material that was available.
i kinda like that allegory, actually. a book is very simple, but a library is more complicated, just like life.
Written in COBOL well before Y2K was a thing
I think they might have left out the situation where you have one condition that's caused by single point mutation so it should be very simple except every single person has a different version of the mutation when they have the disorder! That's what mine is like and because early genetics couldn't individually sequence a whole person, they just spot checked for it and surprise surprise I don't have any of the ones that were known at that time. In fact there's a good chance that if I were to get it done again using the spot check method I still wouldn't test positive for any of them because there's a darn good chance that my mother is what's called denovo which is a spontaneous mutation and here's the crazy part I might be different from my mother because once that spot mutates it tends to mutate additionally. It might not even be on a chromosome anymore, it could be a micro chromosome which would make it almost impossible to detect! On the flip side this type of mutation is what adds material for beautiful and wonderful new features to form on creatures in subsequent generations, it just kind of sucks for me because it makes my nerves a little bit wonky.
@@darcieclements4880 Thank you so much for sharing this! You've given me a bunch of new tabs for things to learn about, as well as just being a really interesting writer!! I hope your wonky nerves don't cause you much pain!
Something about this makes me think of Pratchett, and L-Space!
This doesn’t even cover the impact of gene mapping on law enforcement, justice, and in some cases, righting past wrongs.
It also gave us a whole host of new ethics concerns, and new ways for insurance companies to refuse to cover care for people who need it.
They already do.
And people in camouflage already produce specific agents to affect individual people, or cerntain peoples.
Welcome to capitalism!
The first is true worldwide, but the second is true only in US.
Corpos are gonna corp, as always
in terms of ethics concerns, all that stuff was already there, we just discriminated based on phenotype, rather than genotype. All solvable through proper regulation and once we actually do advance this stuff, there won't be any need to discriminate based on genetic conditions, because they won't exist.
I misread the title and thought it said human gnome experinent and was so dissapointed when I found out it actually said genome.
Gnome? Pff - more like gNOPE!
LOL
You would be surprised to learn then that jokes about gnomes proliferate at NHGRI (National Human Genome Research Institute, one of the National Institutes of Health). 1000 Genomes is an older project. The current one is called, I kid you not, GnomAD.
@@clairesimpson7329 wow
@@clairesimpson7329 No that would not surprise me. MD for 30 years, Undergrad Biochemistry (Aka Molecular Biology in the 1980s) Lol, in 1987-1988, I did manual PCR in the undergrad Research Lab at University of Texas. Micropipettes, small culture tubes plastic 5-10 attached together in groups of 5-10, probably 1-3 ml each max. Heat bath and ice bath with a kitchen timer, lol. IIRC we used Taq DNA Polymerase, but it was a long time ago. Every Professional occupation has their own specialized language with bizarre (to outsiders) abbreviations and lingo. With often dark humor associated with it. The Military has thousands so does science. Medicine also. It is a coping mechanism with high stress jobs. My ex wife is also a MD and we had to be careful with conversations over dinner with others outside Medicine. The Surgeons were often the worst, lol, when the patient was under anesthesia. I remember many of those. As a Medical Student, I just kept my mouth shut, I knew many of these conversations were not acceptable, but context and human behavior under stress is simple reality.
Thanks
I volunteered for a research study that is currently sequencing my entire genome. We’ll see if I regret finding out the things I will find out.
I hoped there was goingto be a cure for my son's primary immune deficiency but he's been gone for 22 years.
I'm so sorry for your loss. We have immunodeficiency in my family Gammagobulin issues... It is still in the study phases!
@@shainazion4073 They did something with genes in Europe like in 2003 or so buti haven't heard much since. Josh had a Bone Marrow Transplant in 1985 but he didn't engraft. He did live till 2002 thankfully.
That's very harsh. I am sorry for your loss, unfortunately it seems they couldn't figure out a solution in time
Science communication doesn't need click-bait titles. To be fair, you can sequence your personal genome and store them in a small pen drive in your wallet in 2016 and now. I'm a geneticist and I have worked with terabytes of sequencing data to know that this is feasible.
Sci-show editors: Please do not interrupt your presenters mid-sentence for a sponsorship ad.
You did not have to choose that point to make the cut and transition, it comes across as disrespectful of the speaker and is disruptive and annoying.
/rant
I don’t think they actually get to choose exactly when the commercials hit, just the number of times.
@@codename495it's not a regular ad, it's an ad edited into the video
Here is-
OUR SPONSOR BRILLIANT!
/s
(although that would have definitely been a better segue than what's in the video)
it completely ruined my attention on the video tbh, i nearly clicked off
@@calvindevries For a bunch of smart people it's curious you don't look for a solution like Sponsor Block and instead shout into the void that is the UA-cam comment section.
As a software engineer looking back on this, it seems obvious in hindsight. If each IF block I made only had a 30% chance of working, of course that control logic would dominate the business logic.
A genetic study, for patients lucky enough to get one (they're expensive) can go a long way in determining what specific pharmaceuticals are appropriate to treat mental health conditions.
I feel like the video undersold the potential of genetically targeted medicine. If I hadn't known about "these genes work better with that medication", I don't think I would have learned it from this video, and I definitely wouldn't have realised that it had more potential than just gene therapy.
A medication for my kid went badly wrong and nearly killed him. We knew immediately that the med caused it, but not why. We were referred to a genetic screening that found he has a mutation in an enzyme responsible for breaking down a category of medicines (including that one). This changed the breakdown speed and meant a slow-release dose will OD him 10 hours later. He's in that list of rare side effects meds always warn about. Because of genetics we know to avoid several medicines with him, not just the one.
General genetic screening would have avoided this, but it's too expensive. Makes me wonder how much the promise of gene mapping wasn't realized because of money, not science.
It will only work if the govenrment spends money on it.
If left to corporations, they will charge an exorbitant price and will take 100 years to make.
@@ericsmith6394 Welcome to capitalism! Profits over People! Heh
And frequently, if drs know what section the suspected mutation is in, they won't request sequencing the whole genome, just that section that they specialize in.
Rather frustrating when there's multiple health issues and having the whole thing would be helpful. Also incredibly expensive at 2k US per round.
10:53 To clarify for viewers who arent familiar with DNA sequencers: That is an Illumina MiSeq, it is not even remotely capable of sequencing a single human genome. For that, you're better off using an Illumina NovaSeq, or if you want something cheaper and low-throughput you could go with an Element AVITI. The MiSeq is better suited for sequencing MUCH smaller fragments of our genome, such as a specific list of genes linked to congenital health conditions.
In fact, that's exactly where DNA sequencing shines in the healthcare field. A cheaper panel of testing to *contribute* diagnoses of health conditions that healthcare providers would otherwise be unable to identify. You can even do it with whole-genome sequencing in more urgent cases as a valuable asset in finding a diagnosis. This video gives the impression that DNA sequencing for healthcare isn't all that helpful, when in reality it is an incredibly important tool in the toolbox of modern medicine. It's not the only tool, but a revolutionary diagnostic tool, not unlike MRI's or X-rays.
There's also several (minimum) days worth of prep before that "wack a sample down" on the sequencer step. (My 96-well 'new to my core lab' protocol RNA extractions were not great today. So a days labor and a couple grand in reagents/consumables in the haz waste bottle. Tomorrow will be better.)
@laurakemp5979 To be fair, it's better to fail at extractions than to fail at library prep or sequencing, but it's still a whole-shift process more often than not
computer code also often doesn't contain helpful little notes 😅
//this bit doesn't seem to do anything but everything breaks if you take it out
Is a comment I've definitely seen more than once. Maybe computer code and DNA aren't so different.
Yeah there's some of us that specialize in dealing with code that didn't get nice little helpful notes and people need it reverse engineered. One of my first jobs was reverse engineering something that was written by a guy who literally was hit by a bus and died suddenly so that it could be documented for long-term maintenance. What I learned on that job was to always make sure everything I produced was well documented in case that happened to me because you don't want to leave your coworkers in that situation.
@@LikelyToBeEatenByAGrueoh yeah I love that, I do prefer and always ask people to put in the specifics of what happens if you remove it even if they can't figure out what the thing does that way if I come across it and I realize what it's actually doing I can update it and same for anyone else who comes across it. Just because you don't know why the piece of code is required doesn't mean somebody else won't have the experience necessary to realize oh yes this is actually doing XY and z thus it needs to be left in. And occasionally you might be able to see that and be like oh it's because this is multithreaded and it should have been single threaded let me fix that fundamentally.
Only when the person making it isn't thorough...or is looking for "job security" by being the only one who can maintain their code. Unfortunately, that can work, and being meticulous (and/or including tutorials in your programs and teaching others how to use them) isn't necessarily rewarded.
At least there was an attempt to fix things.
There were cheaper, simpler and more holistic things that could of been done instead... But were ignored... Things that may have actually worked wonder for human medicine but no one can make huge profits on it so they were never even looked at, if not downright ignored... As always ..
@@peterzotti6430found the crystal healer trying to sell quartz for $50/oz
@@peterzotti6430 And I am a victim, get out of here, I would not be alive and even if I was, I would not be able to type this message, if not for the amazing effort of doctors and researchers all over the world
The biggest and most important thing was finding out WHY certain health issues are passed along. Most people who have celiacs for instance have 2 specific genes in common. But that only is important if those genes get triggered for some reason. But now the trigger has to be found.
We also learned about epigenetics, the switches that do things to genes. That are sometimes inherited.
@@topogigio7031 I'm literally criticizing the for profit medical industrial complex and you're accusing me of being a snake oil sales man... Make it make sense...
Not a failure at all. We simply learned that genetic expression functions much more complexly than we initially assumed, therefore it is taking longer to understand the implications of everything and develop actionable therapies based on the results. I don't think it will really kick off until we have AIs that can continuously simulate genetic expression on digital human models. That will go so much faster than the status quo, where we can only test one condition at a time in organized lab studies that take years to complete. There is also the ongoing ethical question of to what extent we should genetically modify ourselves, which is still unresolved.
No, it is a failure in its own terms. We learned that the central assumption behind the genome project is wrong. You are not defined by your genome. Your mother's life before your conception and indeed your father's life before your conception and your life history in the womb and afterwards are much more important than assumed. We are not mere vessels for our genes, as Dawkins claimed. Epigenetics has destroyed this claim. People who have cloned their pets have discovered this first hand. The clones are different, often very different from each other. People do not have blueprints. It's more like a cake. If you follow a recipe twice you will end up with similar cakes but never identical ones. If you cook one a bit longer or mix one a bit differently it could be tasty or burned. Even that analogy isn't quite right because organisms actually edit their own genomes, they leverage darwinian evolution, for instance our immune system deliberately "evolves" antibodies when we get infected. And this is without mentioning the trillions of other organisms that our bodies are hosts to, all with their own genomes, immune systems etc. AI, no matter how powerful, will never be able to simulate that, it is a chaotic system.
Modifying yourself isn't an ethical question, modifying your neighbor is!
😊
(you used the general ourself as humans, I understood. Extra context incoming. Our genes are modified without recognition or choice by external factors - having a choice is not a morality question, it's a functional one. The options of choice and methods to choose would be an ethical one.)
@@hayuseen6683 I was referring primarily to the scenario of genetic modification for infants. Infants cannot provide consent to genetic modification for obvious reasons, and while most people would agree that genetic treatment to prevent specific genetic diseases would be ethical, going beyond that to other modifications would cause significant controversy. Adults are able to choose to do genetic modification, but the ethical problem then becomes fairness of availability. Wealthy individuals will have much more access to genetic healthcare (or in the future, possibly even physical, cosmetic, or cognitive enhancements) and this can become another form of class-based inequality.
@@Outshinedsg
I figured, though "extent" seems to imply how much, not who gets to do it to who. Some people care about extent - making us less 'human' via transhumanism.
Michael Jackson had the Billie Gene
Is not my lover she's just a
Girl, who
He didn't have her, "she's not my lover"... She's just a crazy groupie. But thanks to genetics, we don't have to take anyone's word anymore.
Hee Hee
Bahaha awesome!
The library metaphore is nice. There are also books in the library about maintaining the library, books about bookbinding, and books that contain instruction on how to arrange the books, scribblings on the walls with bug fixes, etc.
I can’t get over that incredible timing on the ad break, wow
Ray Kurzweil talks about the human genome project in his book "The Singularity is Near". He noted:
1. At the start of the project in the early '90s, critics said that the project would take over 100 years. Kurzweil noted that estimate was correct using the existing technology.
2. The project planned and developed new technologies as it ran. These tecnolgies drastically improved DNA scanning, which reduced the project's time.
3. The project finished early (two or three years ahead of schedule), and below budget.
In its wake, the human genome project left a set of technologies that allowed for rapid and cost effective analysis of DNA from humans and other animals. This pushes scientific research. I assume this also helped with the quick analysis of the SARS Covid-19 virus. Please correct me if I have this wrong.
It’s probably a good thing that it was hyped up like it was, or it wouldn’t have been funded. Framing it as a “big experiment that won’t directly impact patients right away, but help technology evolve. But we don’t know how yet” wouldn’t have gotten peoples attention, or captured their imaginations.
But it was helpful to figure out some things. For example, by looking at a part of code they verified that I have hemochromatosis. Which doesn't need to be rewritten. It just means that I have to donate blood in order to survive. I also love the part about "junk" in the DNA. Because everything in this world works differently than we would think they should. Nothing is as simple as we would love to believe.
Mandatory selfish altruism.
Richard Dawkins approved.
tl:dr It failed in the sense that it over-promised and under-delivered. But succeeded in giving us an understanding of just how bloody complex the genome actually is. And we can do more stuff now.
I wouldn't say this video is too long. Would have been nice if it was longer if you ask me.
@@cedriceveleigh Then this comment wasn't for you. I enjoyed the video actually. The comment was for the courtesy of all of those who are likely to scream "CLICKBAIT"... cause it isn't clickbait.
Science, the proof of the value of failure. Knowledge. 🔬🧪🎉🧠
Failure is only valuable IF you learn from it. Science often does. People in their daily lives often don't.
@jliller that's a bit of a miscalculation too. Without trying again, one cannot be certain a failure is a failure. The confluence of failure is knowledge is more accurate to my point, implying that whomever uses it (individuals or even concepts like science) does learn from it.
"Failure" is a loaded word to use with anything scientific. Like, sure, use it with investors when they were expecting certain technologies/results. But in a scientific sense? The entire point is to develop a hypothesis, test it and see what happens. There is no "failed" outcome. You learn something new either way and broaden your understanding. Either, yes, it works as you think it did and you build off of it. Or, no, it doesn't work like you thought and suddenly you have a ton of new possibilities to consider.
There's no "bad" outcome here.
Okay, that weird editing flub in the hand-off between host and ad through me for a loop. LOL
"Here is..."
---AD---
"...part two of the video."
That's not a flub, it's deliberate.
So it got your attention. Not a "flub".
I'm not a fan. It's jarring.
@@Tfin Umm... I'm still not sold on that one. Maybe it's the possibility of them making an honest error - or maybe more that if it's deliberate, then it's quite tasteless and disrespectful
@@kubadzejkob332 disrespectful? to who?
I think most scientists knew in advance that there was a lot of work beyond knowing the sequence that would need to be done in order to understand the overall physiology.
That "one anonymous sample" was Craig Venter
DNA seems to work a lot like a ROM of a video game. There are functional bits and data bits. And only by understanding the decoder can you follow the code and figure out which is which.
Another major problem was the protein folding project. In order to understand the machines those sequences represent, you have to fold the proteins to see what the machines do. This is many, many orders of magnitude more difficult than finding the sequences. The human genome protein folding project will eventually complete due to the exponential increase of computational power of both hardware and software as a function of time.
P,S. I have many powerful GPUs and occasionally lend them to internet projects such as protein folding for the Covid 19 virus when that was necessary.
This is when you slipped into a straw man argument: 10:11 - no one said "easy cures to everything." They were right that sequencing the genome has opened up new therapies, and tests for diseases. They weren't exaggerating. It's only been 25 years or so.
actually a lot of bad science journalists took comments like we may be able to provide gene therapy cures for some specific monogenetic diseases, and spun them into comments saying that it would be trivial to fix every disease with gene therapy within a few years.
lots of other journalists told equally big whoppers about other aspects of the program as well.
most scientists in the field had more sense.
I don't like calling something not meeting the expectations of people who made stuff up about it on their own a failure when it accomplished its actual stated goal of sequencing the whole genome perfectly
I had my full genome sequenced for a few hundred dollars in 2019. Not quite on the level of “genome in the wallet,” but it’s still pretty incredible when you consider the effort and expense it took to do the first time.
I don't know what computer code you have been looking at must most computer code unfortunately does not contain helpful comments :(
Yeah, most comments are just frustrated devs... And the occasional "ToDo: fix later"
It's frustrating that this video spent the first 12 minutes in the terrible framing of "things are only successful if they lead to immediate clinical benefits" and then crammed in the correct take that "the human genome is necessary to even *start* understanding human biology and that *will* ultimately lead to clinical benefits" at the end. People aren't going to remember the caveat.
I've been hoping for a video explaining just this. And this surpassed my expectations. Well done.
I know the title is meant to get people to click - but so many people only read titles.
As a genomics PhD, the title offends me, and it is a disservice to many people who devote their lives every day to studying the genome.
I get it, you need people to click on the video and engage; I guess the title accomplishes the goal - but at what cost?
Agreed. Video filled with misinformation too, not sure they've ever heard of the impact genome-wide association studies, polygenic risk scores, Mendelian randomisation, have actually had on revolutionising modern medicine and couldn't exist without the human genome project. This feels like poorly researched tabloid journalism
I posted a similar rant before reading your comment. Fellow Geneticist here and I completely agree. In a world that is getting increasingly mistrusting of science, popular science communication channels can do better than click baits
while i agree the click bait tile was bad, i don't think it is fair to criticise the presenter for only doing twice as good as mainstream media with massively more resources.
yes it could have been better, but this is social media, so you have to make sure your expectations are low enough.
@@grokitall science and facts can't change just because it is social media. I thoroughly appreciate the presenter breaking down hard scientific topics and presenting them to a wider audience.
Which is exactly why I'm upset at the needless click bait that can contribute to miscommunication.
@@grokitall Yeah, no. That might fly on Facebook. It does not fly on UA-cam. This site is as much a knowledge resource as it is social media. There are plenty of excellent, well researched videos on UA-cam about this sort of thing. Complaining about it is perfectly valid.
My doctor just ordered a DNA test to find out which drugs will work best with my metabolism. Too cool.
I didn’t hear crime solving (profiling criminals, narrowing down to family tree DNA ) mentioned as one of the things we got out of it
Savannah is a great host! Love their mix of clear and excited communication with a bit of humor and theatrics, keep it up!
I'm pretty sure there are some of my cells on the cards I carry around, so technically there is my entire genome on a card in my pocket. Let's ignore that it'd be there without the human genome project.
Gotta love Savannah, so much enthusiasm and humor, without expense on the science :)
Reminder of the best humanity has to offer in these uber-stressful times :)
Many thanks, much obliged :) :) :) :) :)
5:02 almost as bad ad break placement as daytime tv
As always, I love Savannahs delivery. The humour they inject into the material makes it much more engaging. Keep up the good work, and remember to take your breaks.
in alot of irony this video made the exact mistakes that the earlier scientists made when talking about what the genome actually does!
the genome is NOT a _blueprint_ of a human, its more like a recipe for one (without the picture preview). the difference here is that a blueprint has an end result to be attained but a recipe does not, its just a list of ingredient (the proteins) and instructions ('junk DNA'). on top of that many of the instructions are basically like compiled code, a giant self referential mess of instructions that if followed exactly will make a human but small mistakes can potentially alter later instructions in enormous unpredictable ways.
this is why its been so hard to figure it out, and also why a few diseases where easy; those where part of the ~20K orso proteins ingredient that we can easily see and not the instruction list.
I get what you are saying, but I'm not sure that analogy holds - if I'm not mistaken, recipes typically have an end-result to be attained, or have I been cooking wrong this whole time? 😄
@@caydennormanton9682 yes you have an end result because you have a preview of that, your cells dont have an end result to work towards. that was my whole point
@@sudazima ...and my point is that you don't need a picture to have an end-result, the end-result is just the result at the end of a process, regardless of what was used to make it.
But, alas, my comment was in jest, and I understood your meaning anyway 🙂
@@caydennormanton9682Most people's cannot even properly cook a perfect recipe while having knowledge of how the result should be. Now imagine compiled materials on top of that. I know you got the point already before, just want to say how insane it is our body is even to produce it properly. I for sure wouldn't want to be 'chef' actively having to manage my own 😅
Even when I first heard of the genome project, I knew it was just a first step. If I might make my own analogy, it's like when we first mapped the Earth by satellite. That map helped us out a lot in understanding the Earth but it couldn't tell us where all the diamonds were. There is a lot we still won't know until we actually get there.
"Discovery has no roadmap"
My friends father worked on this project. He died in 2015 from a sudden medical incident. Brilliant, beautiful, family.
A "House of Leaves" reference? You get an A+++! :)
Glad I’m not the only one who got the House of Leaves reference; fantastic read but boy, I wonder how many people are able to get through it
@@stevenkirkwood7039 I'm guessing not many. Few people read physical books anymore, and it would make a Kindle explode... :)
I scrolled all the way down just looking for a House of Leaves comment. Wonderful! I've read it twice
I hope y’all know there’s an accompanying album by Poe (the author’s sister)!
Still inordinately proud I was able to participate as a donor in the HGP :)
Cool! 🎉
This is my first time seeing Savannah host one of these videos. Clearly spoken, pleasant vocal tone, good pacing. Good job.
I don't regularly watch this channel, but her presentation this video struck me as very authoritative and personally knowledgeable on the topic.
This is one of the rare SciShow episodes that leave me with way more questions than satisfying "answers" or food for thought
Hell, even the end of Metal Gear Solid (a game from 1998) kind of goes against the overhyping by people at the time in regards to the Human Genome Project, in a part of Naomi Hunter's monologue at the end of game.
"Each person is born with their fate written into their own genetic
code... it's unchangeable, immutable... But that's not all there
is to life. I finally realized that. I told you before. The reason
that I was interested in genes and DNA. Because I wanted to know
who I was... where I came from. I thought that if I analyzed my
DNA I could find out who I was, who my parents were. And I thought
that if I knew that, then I'd know what path I should take in life.
But I was wrong. I didn't find anything. I didn't learn anything.
Just like with the Genome Soldiers... you can input all the genetic
information, but that doesn't make them into the strongest
soldiers. The most we can say about DNA is that it governs a
person's potential strengths... potential destiny. You mustn't
allow yourself to be chained to fate... to be ruled by your genes.
Humans can choose the type of life they want to live."
I was playing this as background noise while I worked on some hobby stuff, but 8 mins into the vid, I’m asking chatgpt for clarifications of dna, mrna, genome, etc, going into depths of this subject I never was interested in. Good job!
I gotta say, having my entire genome on a card in my wallet sounds creepy and dystopian.
You can have your 23andme app on your phone. Suppose you could share it with your doc
@@DIGIL. That doesn't contain your genome, they just test for specific sequences
"You have genes associated with increased risk taking. Your car insurance rates have been adjusted accordingly."
Only if someone starts using your genome to make clones of you and you want to claim copy right on your own genome but can't.
It’s already on your blood. What difference is a card?
Maybe the best presentation yet! Keep up the great work!
Human genome project is one of first technologies to research in Alpha Centauri(1999y) video game.
Back when i was 17, and studying A-Level Biology, we were told that only when a cell was preparing to divide did the chromasomes form into the familiar X-shaped pairs. Most of the time, they were loosely packed into the nucleus of the cell... and that was all we were told.
Forty odd years later, I finally learned why our genes spend most of their time loosely coiled in the nucleus, tonight. It's so the DNA can be read more easily by the cells transcription machinery! Of course, this may not have been known back then, a case of 'we know what it does', but not 'why'. This situation is common right across all scientific fields, as we make leaps in both understanding and technology.
It was known a lot more than 40 years ago. People picture chromosomes all doubled and packed up with histones and other stuff in that stage of mitosis because that image is the one where they are most visible in a stained slide under a light microscope. Most of the time they are unravelled, accessible to replication, transcription and repair mechanisms, as well as factors which block some sequences, or how could they work? That's why they are only visible in mitosis, when they will have to migrate to the two halves of the dividing cell without getting tangled or mis-sorted.
it seems considering its sequel project encode is still ongoing that is not much of a failure and more a thing of "it turns out its much more complicated and nuissanced than we though, what we have is mostly useless... because we don't understand it yet"
Deep Thought vs’ the Earth time then I guess.
@@martinsmallridge4025 only if you are a pan-dimensional lab rat 😁
While it probably was a nuisance, I think you meant "nuanced" 😉
@@caydennormanton9682i think i prefer his version though 😅
I was NOT expecting a House of Leaves reference, nice one!
"To map the very stuff of life; to look into the genetic mirror and watch a million generations march past. That, friends, is both our curse and our proudest achievement. For it is in reaching to our beginnings that we begin to learn who we truly are." -Academician Prokhor Zakharov, "Address to the Faculty"
"We hold life to be sacred, but we also know the foundation of life consists of a stream of codes not so different from the successive frames of a watchvid. Why then cannot we cut one code short here, and start another there? Is life so fragile that it can withstand no tampering? Does the sacred brook no improvement?"
~ Chairman Sheng-ji Yang, "Dynamics of Mind"
"The genetic code does not, and cannot, specify the nature and position of every capillary in the body or every neuron in the brain. What it {can} do is describe the underlying fractal pattern which creates them." - Academician Prokhtor Zakharov, Nonlinear Genetics
The bubble bursted and sparkles came down in style I love science 🧪
I have a sort of metaphor for this. It's like a computer wrote it's own program in assembly code without human readability in mind. The situation is kinda similar to PvZ modding in a hex editor. We kinda just have to guess what each bit does, and write down how it effects the game when changed. Maybe someday we can learn how to "program" a genome, that would be interesting.
It is assembly language code for a self assembling machine.
My friend has sons and brothers with Partington's syndrome, a disorder directly linked to a specific gene mutation on the Y chromosome. However, each son and brother is a unique person with variations in cognitive, muscular, and speech (etc.) difficulties associated with the mutation. They also have a broad spectrum of personalities, and it is clear how environmental factors have affected them, such as different parenting styles and choices in educational resources. My point here is even knowing the exact mutation on a gene doesn't tell the whole story of a person. I am so glad we are still studying, still learning and still caring about all of it.
I clicked on this video misreading the title as the human gnome project. Kind of disappointed there wasn't some secret project to make us more gnome like.
🤣😂😅
Jan Jansen, at your service
Oh, no, those little guys might be perverts! What could be under their hats?
Excellent explainer of a complex story. Thanks!
I think it's worth mentioning that like. as far as i know, as of right now, even one-gene-zebra conditions like *mine* can't really just like. be edited in a living organism like those promises implied. like you can't just graft a working copy of a gene into a patient who didn't start with one, even if you know exactly which gene is causing the problem.
A few such conditions have therapies now by removing some cells, patching a good copy of the gene into them using a viral vector and returning the cells to the patient. Mostly it's been done for quite rare conditions, but recently two gene therapies for sickle cell anemia have become available. One patches in genes for normal hemoglobin, while the other reactivates the production of fetal hemoglobin. While these therapies are expensive, they may be less expensive than repeatedly treating e.g. sickle cell crises.
I hope something will be developed for your condition. Keep up with the research and there might be a clinical trial you can join.
Acquiring knowledge is never a waste of time, money or effort.
Hey, you knew you were putting together a commercial. Why did you cut off mid sentence?
The bit about all metaphors being somewhat fictional is super important. One of the coolest assignments I had in grad school was talking about the potential misunderstandings and misconceptions that come from calling CRISPR a "gene editing" tool
It sucks to read uncommented code. Pffsh
Excellent summary. Me, Molecular Biology undergrad (it was called Biochemistry degree in the 1980s), to Med School, 30 years as a MD, PCP, Family Medicine. The Human Genome Project was the easiest. The "low hanging fruit". Never lost my fascination with Molecular Biology and tried to keep up with advances over time. Sequencing the Genome was very scalable and with computerization and technology advancing was completed quicker than predicted. LOL, I actually did manual PCR as an undergrad, Micropipettes and small culture tubes, heat baths and ice baths using repurposed manual kitchen timers. Took Molecular Biology in my 2nd year at MIT, taught by Harvey Lodesh, from Preprints of the 1st edition of Molecular Cell Biology, he sent all the students a signed first edition, kept his promise, I still own it. Dr Lodesh is still working, a great teacher and a great human, would talk to him after class many times. A true research scientist and a Great teacher, unfortunately not that common anymore, publish or perish right? The Human Genome Project was the easy part and was definitely overhyped. But it was a start and had to be done and paid for. Now the really hard work began, proteomics, regulation of gene expression in different tissues, in health and in disease states, RNomics, etc. It will take a long time to figure this out. Humanity has scratched the surface, but the really hard work is not "low hanging fruit" we are beyond that. Great vid!
Big scientific and engineering projects present huge up sides for over-promising and scant down sides. So not seeing big surprises here. The details are fascinating nonetheless.
most pure science projects return 7 times more money than was spent on them as direct benefits, and often a lot more with indirect benefits, you just don't know where the gains will come from.
this is why you promise benefits, but are light on specifics and you make sure not to over promise on specifics.
Savanna is so easy to listen to and understand, thank you for being a great host.
All the best Jules 💕
So HGP was not a science experiment, but an engineering project. Sounds good to me.
Ironically, some of the tools we got out of the HGP were sequences of non-human organisms, like E.coli and fruit flies, the idea being to develop techniques in simpler genomes before progressing to more complex genomes (us; we are the more complex genome). Sequencing those other organisms has also contributed to medical advancements because there are just some things we'll never be able to study in humans (like the genetics of development).
The more you know, thank you science.
To grasp and understand your own errors and mistakes is not a failure
I was part of the human genome project cause my brother and I are Identical twins!
You are awesome and we appreciate you Savannah! Thank you!
PS: so is your shirt!
Hi Savannah!
I love the library metaphor.