Down syndrome reversed in newborn mice with single injection | Hacker News Reader

Down syndrome reversed in newborn mice with single injection

abc.net.au

258 pointsuptown114 comments

A good submission. The article is appropriately cautious about reporting on a preliminary research result in an animal model. That's refreshing. It helps HN discussion to submit actual NEWS articles by professional journalists rather than recycled press releases from PhysOrg or ScienceDaily. As usual, much more research will be needed before this finding could possibly be applied to human medicine, but it suggests new approaches worth investigating further.

So, what's a good replacement for PhysOrg?

http://www.reddit.com/r/science is actually pretty good about calling out unscientific journalism, making it a somewhat-decent source of science news. (As long as you read the comments.)

I strongly disagree.

r/askscience is great. r/science is not science at all. Take a look at the top-voted story at the moment: http://www.reddit.com/r/science/comments/1lruai/lsd_could_be...

That's far from science. Half of the comments are just anecdotes.

Actually, that link proves my point. For example, this comment chain: http://www.reddit.com/r/science/comments/1lruai/lsd_could_be...

That's the #2 comment, and it's a link to work cited in the article. And the top reply to that comment is from a psychiatrist who gives a thorough (and thoroughly skeptical) breakdown of the science behind the cited work. I'd say that's a grade-A analysis.

Sure, you can find some great bits of information there, but when it comes to something like a science subreddit, you have to be very strict in moderating comments that might mislead people (r/askscience does this very well). There is NO room for anecdotes or personal assumptions when it comes to discussing scientific articles. It really is all or nothing, if you allow any non scientific-based discussion, you get something like r/space which is (was?) one of the worst subreddits in my opinion.

Also, there is a huge political bias over on r/science. I see this as a huge problem with most of reddit actually, but people should forget about political bullshit when it comes to discussing scientific facts. Unfortunately, this is not the case and people begin to discuss the moralities/logistics of drug legalization rather than discuss the science presented in the article. I have gotten into many debates on that subreddit and have, attempted to, correct so much misinformation that I was just forced to unsubscribe a few months ago because of how rage-inducing it was. I'd stick to r/askscience.

/r/askscience is infested with a bunch of literal-minded and narrow-minded individuals, with groupthinkers, and with group-up-voters and group-down-voters. Heaven forbid you use a metaphor to make an abstract concept easier to understand. It's like preaching to the "Bible is literal truth" crowd.

It definitely has its flaws, but I think it is still one of the better places to get a good answer to a random science question on the internet. The community is huge, very active, heavily moderated, and it has some really great answers.

It's not as rosy as you make it seem.

Right now there's a thread there discussing the lens size and resolution for some camera phones. There was a reply that had 5 up / 0 down votes when I got there - and it was derived from a pretty naive error. Yet it was deemed "best answer" at the time, according to the votes.

This situation is not unique, it happens all the time on /r/askscience. Semi-educated loudmouths are a huge fraction of the contributors. Occasionally you get a real expert chiming in, but their stay is typically limited. Many gross errors go unchallenged forever. Voting is dominated by groupthink. Goes on and on.

If you think that's "one of the better places to get a good answer to a random science question on the internet", then you have some exploring to do yet. ;)

I was glad to upvote your follow-up question about better sources. I have not tried the Reddit group mentioned in the other reply you received, but the characteristics mentioned there sound helpful. I earlier posted a reply here on HN

https://news.ycombinator.com/item?id=4735122

listing some of my favorite sources for science news. If I see a link (say, from my Facebook friends) from PhysOrg or ScienceDaily, I NEVER assume that it is worth submitting to Hacker News. (Longer story about that by request.) If the recycled press release looks interesting and plausible, I try looking up the name of the study author or key words from the study findings and see if I can find a better source.

Lots of good stuff there, thanks.

Thank you for this submission.

Summary: The size of the cerebellum in most people with Down syndrome is about 60% of normal. Researchers at Johns Hopkins University School of Medicine were able to achieve normalized cerebellum growth in Down-syndrome-like mice by treating them with a sonic hedgehog pathway agonist at birth. Not only did this single shot normalize cerebellum size through adulthood, it also resulted in improved cognitive abilities usually associated with the hippocampus. These improvements may have been due to a strengthening of the communications between the cerebellum and the hippocampus, according to Roger Reeves, Ph.D., a professor in the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine.

What if they administer that to normal mice? Will they talk?

They may also escape from their cage each night and try to take over the world.

Or escape and move to a farm and create a tech utopia and help out widowed mice in their spare time?

( http://en.m.wikipedia.org/wiki/Mrs._Frisby_and_the_Rats_of_N... )

Wow, seriously loved this book. takes me back. Thanks.

Thanks for the summary. So they're basically treating a (albeit important) symptom of the trisomy.

That's my interpretation of it as well. They are not actually repairing the chromosomal abnormality, they are addressing its effects on brain development. So I presume a treated person would still have the physical appearance characteristics of Downs as well as the other health issues (I believe people with Downs syndrome are much more prone to heart disease or problems).

I also wonder if the brain growth would be permanent (remembering Flowers for Algernon)

> On the day the mice were born, scientists injected them with a small molecule known as a sonic hedgehog pathway agonist.

Obviously I had to investigate a gene called Sonic Hedgehog and how it could come to have such a name. From the wiki[0]

>The hh loss of function mutant phenotype causes the embryos to be covered with denticles (small pointy projections), resembling a hedgehog.

I'm glad to see a lack of temerity in a medical article, especially when the results seem so very promising. Nonetheless this is a really great result.

The names get sillier: there's a sonic hedgehog expression inhibitor called robotnikinin, after Sonic the Hedgehog's nemesis Dr. Robotnik.

I was sure you were joking until

http://www.techtransfer.harvard.edu/technologies/tech.php?ca...

http://en.wikipedia.org/wiki/Sonic_hedgehog#Robotnikinin

That gene as the wiki article notes is an example of why generally things in the medical community need to be given serious sounding names. No one wants to hear that the thing killing or making their child unwell has a silly name.

On the other hand, you can get so serious that it becomes comical again. Much laughs were had in 5th grade about the endoplasmatic reticulum, out of no reason beyond being a 5th grader. On the other hand, that's one of the only cell parts I still remember.

Even better: I called one of my classmates a homo sapien, he went to the teacher and complained (he thought it meant he was gay) and the teacher said "you are a homo sapien". Ah, 6th grade, good times.

Did this happen in every 6th grade? Or did we both know a guy named Walter?

Nope. that happened in my 6th grade as well. We had particular fun with "homo erectus".

Ha, never heard of anyone else doing this before.

Churchill would have agreed:

"Operations in which large numbers of men may lose their lives ought not to be decided by code-words [...] of a frivolous character, such as 'Bunnyhug' and 'Ballyhoo.'"

The silly names almost always start from the fruit-fly community. They have some of the craziest names, but they are usually derived from the resulting phenotype. However, the fruit-fly version is just called hedgehog (hh), because it results in the fruit-fly embryos looking all pointy.

In this case, the funny name was added by vertebrate researchers who ran out of names when they found 3 homologs. The first two were named desert hedgehog (DHH) and Indian hedgehog (IHH). Naming the third Sonic was just too irresistible.

Drosophila names are truly the best.

Contrast that to C. elegans naming: dpy-5, let-37, unc-11, egl-2. The prefix means something ('unc' is uncoordinated) but otherwise very bland.

Those names may be funny, but they are really annoying if you try to do NLP...

Does the DSCAM gene (Down Syndrome Cell Adhesion Molecule) fit into this picture at all? This gene is very unusual, as it gets spliced 38,000 different ways with different variants in different neurons, allowing the brain to get wired up correctly. (It's like being able to give neurons in the developing brain labels to keep track of where they go.) Since this gene is in the part of chromosome 21 that causes Down Syndrome, it seems to have an important role in Down Syndrome. But I don't see any connection between it and the current paper.

Any experts who can explain more? When I read about this gene a few years ago, it seemed like a key to explaining how the brain is formed, but I haven't seen much about it since then.

>There is no cure for Down syndrome

I would like to point out that it wasn't fully reversed, but some effects of down syndrome were reversed. Still very awesome.

This is very encouraging and I appreciate that it doesn't set artificially high expectations for it working in humans.

And I think I can claim learning my something new for the day in finding out that something like a sonic hedgehog pathway agonist exists.

Geez, does nobody read Flowers for Algernon anymore?

I thought the exact same thing!

Don't be afraid. Flowers for Algernon is a touching story and a good warning, but it doesn't mean there should be any "no-no zones" in science. It's just you don't start with humans.

My reaction was: and does it wear off slowly?

The paper itself is here: http://stm.sciencemag.org/content/5/201/201ra120.full

This is good news, and research to help prevent, treat, or cure Down's Syndrome is probably a good thing.

But I'm gently squeamish about it. I know many people who have Down's Syndrome (and other learning disabilities) and me welcoming this research feels a bit like me saying those people should not exist.

That's an extremely odd attitude.

It's like the "cure" for the mutant gene in X-men. Saying it needs to be cured can be interpreted as saying "it's bad that you have Down's Syndrome". Giving someone enhanced mental capacity would certainly help them, but I think for someone who's used to accepting and loving others for who they are, it isn't necessarily odd to have an uncomfortable reaction to the idea of "curing" them - even if, objectively, it's helping them.

It relates a bit to some of the discontinuities that have occurred between deaf communities and researchers working to correct the issues. Cochlear implants were not seen as a positive development by some (many?) deaf people.

The same attitude will have to be dealt with, to some extent, with anything that significantly alters a persons sensory or cognitive ability when a culture has developed around those limitations.

Actually there's a similar attitude in the culturally Deaf. Their identity as it relates to their Deafness means that they even look down on those who try to make accommodations with having any hearing, the worst being a cochlear implant.

https://en.wikipedia.org/wiki/Deaf_culture

No, it's saying that you'd be happy if those people didn't have Down's Syndrome, and all the difficulties and health problems that go with it.

I have a cousin with Down's syndrome, and he is a delight.

Nobody here is saying that people with Down's shouldn't exist. We're saying that their lives would be easier and more productive if they didn't have impaired cognitive function.

They would still exist, just without Down syndrome.

Are you worried about cures for cancer because it would be saying people without cancer shouldn't exist?

Are all neurological disorders like cancer? How do you apply this to autistics? Is our perspective on the world and our specific neurology a feared disease, should it be? DS people ask very similar questions.

I have a friend that has chronic pain. I'm all for treating the chronic pain, yet I don't feel like the friend should not exist.

Down's Syndrome IS a bad thing. It's a disability that inhibits their ability to function in society, and affects their physical health as well.

I can't imagine that anyone could possibly be worse off for having their case of Down's cured. That's not incompatible with accepting them for who they are with the disease.

Here's a thought experiment for you: Suppose your son, a DS patient, rejects the treatment on the grounds that they like having DS. As their caretaker, you have two choices.

- You can force them to submit to treatment, reasoning that their cognitive deficiency keeps them from understanding the implications of rejecting the treatment; or

- You can allow them to forego treatment and thus bear the (in your view) increased burden of taking care of them.

I ask out of curiousity rather than judgment. Which would you choose and why?

There is a third side to this: Increased self-awareness. This treatment only caused the brain to develop normally, which would mean that in the case of humans with Downs the other downsides to the disease would remain (until another cure/treatment was found for those as well, of course.)

Would a person with DS who gains normal brain function really be better off afterwards? Would a large segment of the patients fall into depression? I have a brain damaged uncle and know just how much verbal/passive abuse these groups get in their day-to-day life, luckily in his condition it doesn't really get to him like it does a normal person.

This is a very good point. I remember watching a documentary a long time ago in wich people with DS but only moderate mental retardation became fairly frustrated with the fact that they looked/were different and wanting that to change.

Well, I'm not a parent, but I think I would choose the former. I think they're probably unable to understand the implications, particularly if it's a treatment that has to be done at birth, and I think my judgement is better than my young child's in any case. And it even helps my selfish side, because, as you point out, it makes it much easier to take care of him.

Ask this about autism and see what kind of "caregivers" are out there. Or, if you as a parent could not get services for your DS or autistic child, would you get a lighter sentence for the all-too-common DS and autistic murders out there? [The press treats caregiver originated murders gingerly too.] Autistic rights groups follow these developments painstakingly, often in dread of what the wider public incorrectly assumes from these very basic studies.[I hate science sensationalism with a passion.]

The book: "The Speed of Dark" by Elizabeth Moon has a similar theme to your question (but deals with autism, not downs syndrome).

If you were advocating for killing them then yeah that feeling would make sense. As it is, you are saying you would like their disability to not exist, which I hope is the case.

> I know many people who have Down's Syndrome (and other learning disabilities) and me welcoming this research feels a bit like me saying those people should not exist.

I was waiting for this sentiment to appear. I think if you carry that to it's logically extreme you'd also be against teaching them life skills and training to make them more independent because that would change who they are.

To be blunt, it's better than crushing their skulls and ripping them apart limb from limb, which is the preferred approach to dealing with people with Down's Syndrome in many countries at present, including the US.

What? Can you elaborate?

I think he's using colorful language to describe the process of abortion.

I think it's a reference to abortion.

My brother has DS. I don't think we should fetishize neurological disorders. It is a heartbreaking disease: watching him lose the ability to communicate effectively with the world and withdraw inward has been the hardest thing I've had to see. DS cuts people off from the world and isolates them; no one should have that kind of loneliness and alienation forced on them.

Also, let's be clear about this: people with DS have a very high incidence of early dementia and Parkinson's disease. If we had a neurotypical group of people that had a mutation that caused a similarly high incidence of early dementia and Parkinson's, there'd be zero hesitation about treating them at birth so that they wouldn't have to suffer from dementia at age 35.

Autism is labeled as a "neurological disorder", do you like to apply these opinions to autistic people who want to keep their selves that have thus far developed? You "cure autism" and you remove all of the interactions that person's brain had with the world around them and the perspectives their neurology causes [?].

People with Down's Syndrome don't live very long. It's more than just a mental disability.

http://en.wikipedia.org/wiki/Flowers_for_Algernon

An equally interesting question is, what would this injection do to people (or mice I guess) who are born without any deficiencies?

You can guarantee a genetically normal (there must be a better description) foetus will get injected if a treatment like this came to exist, so this is a good question.

Parents should be allowed to opt-in for experimental treatment with this. What could be learned from just a few real human tests could outweigh years and years of purely academic study and potentially lead to real treatments decades sooner.

This is an interesting step. If we manage to use techniques along this line to cure Down's Syndrome, I wonder if the next step another decade onwards wouldn't be intelligence enhancement.

As someone whose brother has down syndrome, this is one of the most exciting things I've seen on HN in a while. Thank you for posting.

Sooner or later there will be a new better breed of humans. I say within 50 years.

How does this work on normal new borns? Super humans?

This reminds me of Flowers for Algernon!

I'm going to try and say this in the most warm and well-intended way possible.

I wonder how long it will take before someone from the Christian right claims that if science can reverse DS in mice that it won't be long before we can reverse "gay" in people.

We probably will be able to reverse 'gay' in people. We'll probably also be able to reverse 'straight' as well. I've seen some sci-fi that touched on this subject a bit.

http://en.wikipedia.org/wiki/The_Forever_War

I'm pretty sure even political inclinations could be flipped over, provided we dig deep enough into the "machinery" up here.

That's interesting to think about. On the one hand, it sounds absurd to say that a medical procedure could influence someone's future political beliefs. On the other hand, would that sound absurd in 1,000 years? We're really in the very beginnings of understanding the human brain.

I'm not a doctor, but I could probably influence someone's political beliefs through medication, at least for the duration of treatment, and probably with aftereffects lasting far longer. $20 per treatment, several treatments per month. ((RS)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine)

I absolutely love that book. One of those novels where I was really emotionally attached to the characters. The social and scientific ideas Haldeman touched on were very eye opening.

I actually just started reading it last week, I'm a couple chapters in and it has me hooked. Glad to hear other people have enjoyed it the whole way through!

I took a sci-fi writing class from Haldeman in college. He was great.

Someone can always claim that. So what? No matter how loud a megaphone they get it won't make them right.

Fair point.

I really don't see how this comment belongs here.

Is mild Asperger's a deviation that should be corrected as well? What about people that are border-line Down? Or just a bit smarter than that?

Next we'll be correcting minor things like vision and hearing! Where does the madness stop?

Or major ailments like being dead -- perish the thought!

If you are talking about anything caused by our genes someday we could all be just a few approved clones of what the people in power think is "best". Over-correction of natural variation can be dangerous for a species' survival. At least this author thinks so: http://www.amazon.com/Children-Of-Prometheus-Accelerating-Ev...

Interestingly, if being gay is a biological phenomenon rather than a social one, then that may be possible.

I wonder if Wikipedia has a list of unethical medical research topics?

My gut feeling is that the majority of homosexuals are social, rather than biological.

So when did you choose to be (presumably) straight?

Silly rabbit, there you go thinking again. Did I say they chose? No, I said social, meaning their homosexuality was caused by social pressures instead of biological imperatives. I am sure there are some that 'chose' to be that way, just the majority of them are that way because of imprinting or other social pressures.

> being gay is a biological phenomenon rather than a social one

I would expect it to be a little of both. We are very complex animals and not all our social aspects are purely social rather than biological. Think bonobos and chimpanzees.

How long till we find out the NSA has been doing this in secret for years?

This is the most 'warm, well-intended way possible' to divert the discussion to something entirely unrelated and SNR-destroying.

I don't see how considering the social implications of scientific change is a diversion, YMMV.

Well at some point, once the "mechanics" are mapped out, the ability to 'change' anything will be possible. I expect that schizophrenia and other mental disorders will top the list but as the technology is refined, adding creativity and intelligence won't be that far behind. I don't expect to live to see it but I can imagine that if the world doesn't spasmodically revert to the dark ages my kids will see it.

Eventually we might have the ability to choose gay, straight or whatever. Perhaps as easily and (non)permanently as coloring ones hair today. I think that would be an awesome future.

Isn't the biology that makes a person gay or not set at birth or in the early years? If so, treatments that provide a one-time change to gay or straight would probably come first.

The social implications of that would be interesting. How will people react when gay parents choose to make their in-vitro or adopted children gay? Conversely, how would the gay community react if no more gay people were being born?

I don't think we really know. There is some evidence that you are "born with" your sexual orientation, some that it is shaped in early childhood, some that it is due to a mix of factors (e.g. a predisposition and a "trigger"). But I readily admit I don't follow research in this area.

/* Am I the only one here who misread the title initially as "...with singleton injection"? */

Headline grabbing from some researchers who are probably trying to preserve their funding.

Some mice were genetically engineered to suffer brain shrinkage, this injection partially reversed that. Downs's syndrome is a genetic abnormality which affects many aspects of the brain and the link to Down's syndrome here is entirely specious. The claim is as idiotic as observing that people sometimes die from incisions, so reversing the effect of an incision by applying a sticking plaster is heralded (with caveats of course) as being a way to reverse death.

Oh, and it is Down's syndrome, named after John Down.

It's funny because you said Downs's syndrome the first time.

and it is Down's syndrome, named after John Down.

The preference in the international medical literature is to name syndromes WITHOUT the possessive suffix on the name of the discoverer, partly because languages don't agree on what grammatical ending to use to indicate genitive case. Thus the standard name of this syndrome, for people who don't more descriptively say "trisomy 21," is "Down syndrome," without the apostrophe-s ending.

https://en.wikipedia.org/wiki/Down_syndrome

https://en.wikipedia.org/wiki/List_of_eponymously_named_dise...

I'm not conversant with the 'international medical literature' so I shall assume you know what you are talking about. However, I don't take wikipedia as an authorative source on anything.

I disagree. Wikipedia links are very good, specially for informal discussions like this one.

- The content is readable by most people without having to have specialized knowledge on the subject.

- The content is open and reviewed by multiple people.

- You have links to the references. In this case there is a link to this NIH article. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667526/ But the content is more technical and harder to read for most people.

I said it wasn't authoritative, I said nothing about readability or openness, neither of which have anything to do with what is under discussion.

I can provide plenty of UK links which refer to Down's syndrome.

I'm a Wikipedian, and I'm fully with you in not taking Wikipedia as authoritative about much of anything, because I have seen how the sausage is made at Wikipedia. That said, after a Google search, I saw that the two articles I linked to showed that many medical syndromes are named without a possessive ending on the personal name associated with the syndrome, including Down syndrome, and that was the immediate point at issue.

By the way, I try to light a candle as well as curse the darkness at Wikipedia, by gathering lists of good sources for all the Wikipedians to use,

https://en.wikipedia.org/wiki/User:WeijiBaikeBianji/Intellig...

https://en.wikipedia.org/wiki/User:WeijiBaikeBianji/Anthropo...

and by updating articles that have long been tagged as needing improvement.

https://en.wikipedia.org/wiki/IQ_classification

I wish that Wikipedia were much better, but the current way to make it better is for people to roll up their sleeves and do something about making it better.

Same with "Tourette Syndrome". It took a while to get used to, but it makes sense.

> The team at Johns Hopkins University of Medicine, in Baltimore, used lab mice that were genetically engineered to have extra copies of about half the genes found on human chromosome 21, leading to Down syndrome-like conditions such as smaller brains and difficulty learning to navigate a maze.

So they are attempting to build DS into mice and then mitigate the damage caused by their "DS like" enhancements to mice. Sounds like the right path to a solution to me.

Catchy title's make the front page. Sure they may have misled the readers a little bit, but if you read the entire article you can typically criticize the title. They definitely could have named it better, but balanced with the content I think it was appropriate.

Also https://en.wikipedia.org/wiki/Down_syndrome. I'm not saying that Wikipedia is the definitive answer on spelling, but it does give them at least some footing for their spelling.

Edit: tokenadult has a much better answer on the spelling than I do, his comment wasn't there when I starter writing this though.

They did not build DS into mice, they created one of its symptoms which they then reversed, hence my comparison to exaggerating the effects of sticking plasters. The mice did not have anything like DS and claiming this experiment as having anything to do with DS is sensationalist exaggeration, in fact it is borderline dishonest.

So what would be required for the mice to have something sufficiently Down's-like? They didn't shrink the brains with toxins or anything, that shrinkage was a natural consequence of duplication of genes, just as it is in human DS.

Some genes, not all of them. The experiment was about brain shrinkage, not Down's syndrome.

The mice are made specifically as an animal model of Down syndrome. See http://dmm.biologists.org/content/4/5/596.full

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