Choosing the genetic future for your children

[J11]

I am interested in hearing from members of this forum on the topic of genetic selection.
Whenever the topic is discussed, it does not take long before strong anti-eugenics arguments appear.

However, many members of this forum are 44 genotype and this confers a substantial risk of AD ( though
hopefully help is now on the way with the new forum Buck project).

Have or would you use a genetic selection technology that would select against a 44 child?
As a 34, I do not know whether I would select in favor of a 33. Strangely, in my family the members without
a 4 are the ones with dementia and the ones with a 4 are the ones without dementia. It would appear that for men a 4 is not a large AD risk enhancer. My 23andme Alzheimer risk report has been slowly moving downward.

Considering that many genetic illnesses (possibly including AD) might involve the combination of many small genetic risks, it would be interesting to hear what genetic technologies those on the forum might suggest that could reduce the genetic risk of diseases (including AD), if many alleles are involved. Perhaps the genetic selection of individual chromosomes from egg and sperm cells? Currently genetic selection technology is quite limited and is only used to select against simple single allele illnesses.

Any comments?

[LanceS]

Don' t mean to hijack, so sorry if it appears that way.

When I briefly read about the Biogen, alzheimers drug it appeared to be some sort of antibody that "attacked" or perhaps better "neutralized" E4 protein beyond the blood brain barrier. I had no idea it could be possible to have that and no side effects (color me skeptical, color me been there done that). No side effects to me means no body autoimmune issues, no brain autoimmune issues, and no issues with further "clogging" or "collapsing" of the "tributary of tau and AB clearing".

Can this drug can be that drug? There seem to have been many failures and now one that at 52 weeks they have some hope. The difference between the E4, E3, and E2 proteins are so small and our ability to target these proteins with therapies is increasing. So I dunno. Seems like a possible MiracleDrug1.0, should it get beyond the next barrier of phase 3 clinical testing.

But maybe thats what we end up doing? Taking certain drugs that reduce the implications of our genetic individuality to the point where the physiologic side effects are worth the benefits. In a sense we are reducing our genetic individuality in much the same way you are talking about.

I think I'd be ok with that if we were very careful about telling people about what the negative implications were. Right now we have a bunch of good looking pharma reps running around regurgitating stuff that is made up by lawyers, marketing, public focus groups, and heavily stock incented businessmen. And our doctors aren't educated or motivated enough to see through the nonsense.

So I dunno... not sure I see us being able to switch out that 54th element of the E4 protein with some kind of genetic eraser in our lifetimes (I am very new to studying biology so FWIW)... but I could see us accepting some trade-offs where we can accept some negatives to go with the positives. I would love to think our government would let us do this and help us do this. I am not sure they do a good job today. E4s seem to be different and to the point of many recent posts, some of us E4s respond in dramatically different ways to external, internal etc stimuli. Figuring all that out is becoming possible, but given our state of the "patient-doctor" relationship, I see no way this can be effectively scaled and implemented.

I think we're going to need lots of innovations similar to Theranos... like that on steroids... linked in with our phones of course (which are probably causing lots of issues)... so that the scalability of the petri dish testing environment can be replicated in the human body. So we go in to a docs office they run some tests, quantify likely benefits, quantify likely negatives, and we get to roll the dice on the type and quantity of the drug we want. How fast can we get there? Maybe for our kids. This FDA thing places a priority on safety when sometimes for certain diseases, the priority has to be innovation and personal choice.

As for my kids. They will solve these problems for us ; ) So I tend not to worry. But when I see how their beautiful brains soak up sugar and how they crave more. I think about slightly ketogenic diets for them at earlier ages. I haven't tried to do the due diligence and am ketogenic because I am still losing weight. But I wonder if the e4 brain in all its beauty can't be embraced by lifestyle changes and maybe those lifestyle changes can be good for the whole person no matter the age. Sometimes a burden borne by someone becomes something beautiful that benefits everyone. Not yet willing to say that E4s should be switched to E2 with a little yellow pill. Certainly when you look at societal costs, E4s seem to be a very high cost model. But I think we should be able to reduce those costs in the coming years which will be great for the kids.

[Welcomeaboard]

If the 4 makes a person different than a 3 or a 2 in how they think, then I think not as I like the way I think.

[J11]

I am interested to hear from other forum members on this because we are all very aware of the consequences that a 34 or 44 genotype can have (and is having) on our lives. It has been over 30 years since widespread genetic counseling has resulted in large declines in the rate of some childhood mono-genic illnesses. My impression would be that the rate of 44s has not changed substantially through time. There has not been
the same organized effort to address this problem as has occurred with childhood genetic illnesses. In fact, there is still considerable resistance from the diagnostic sector for people to even learn their APOE status. 23andme has only recently provided this genotype. At the same time, the risk for someone with at least one 4 having a 44 child is substantial.

Most members on this forum probably have a fairly good idea what genetic changes could allow the next generation to be dementia free. However, on some dementia websites many commenters had never thought of
using a genetic selection technology to prevent transmission to their children. Even medical doctors preparing for parenthood while facing serious genetic problems seemed largely unaware of the technology available to them (e.g. IVF, pre-implantation selection, etc.).

[J11]

After the exome scan, I have been able to access different software packages in order to try and understand the results.

One of the software programs allows users to construct networks for genes, diseases, supplements etc. .

The program offers 2 initial networks for AD (you can add different elements from there). If anyone is interested, I could upload other AD networks. I found the network with the supplements especially interesting.

I have attached one of the basic views for AD.

Alzheimer 1.PNG

[J11]

I know everyone wants more of these network pictures, though no one has asked. So here's another.

This one is for the second gene network description of AD. In this network, small molecules that interact with the genes in the network are included. Notice that at the bottom simvastatin is shown interacting with HMGCR
(not so long ago HMGCR variants were big news on this site). Surprisingly, EGCG and curcumin are not included on this picture, though when the network is enlarged, they are.

Thinking in terms of networks is a great way to understand complex disease processes such as AD. This is the logic behind the Buck project.

Alzheimer 2 Supplements Small 1.PNG

[Hepoberman]

Throughout the ages our offspring's genetics were determined by our desire for mates with large breasts, a strong butt, toned muscles, and sometimes even intelligence.

In the future we will use a dating system that properly aligns us with a mate that has compatible genetics and reduces the chances of detrimental genetic combinations.

My wife is a 2/4 and I am 3/4. We probably wouldn't have been matched.

There are many, many genetic diseases that could all but be avoided with intelligent gene selection, even now. Just imagine where this is heading...I wonder what my perfect genetic match would be?

We can't stop the big wheel from turning, we might as well endorse it. I would encourage my children to sequence the genes of any potential mate before copulating.

Hep

[Stavia]

J11 - there are so many facets to your question. Ive been pondering it at times during a crushing schedule at work. Its ethics meets functional optimisation head on.
Stephen Hawking would have been selected against was one of my thoughts.
Im not religious at all (athiest) but live and work with strong lifelong ethical underpinnings and have often pondered the ethics of decisions around terminating a Downs child in deciding that child is not fit to live.

Would I do preimplantation screening to discard an e4 embryo if I were having another child? No
Would I, an e4/4, want to have been selected against? No

I think we've opened Pandora's box and now events will hurtle along. Possibly to good places, and some bad....

[Julie G]

REALLY, interesting question, J11. I've been thoughtfully pondering it ever since you've posed it. The younger me would have eagerly jumped at the chance to have a "perfect" baby, but almost 53 y/o me wouldn't trade my imperfect 3/4 baby for all the tea in China- spoken like a true Mommy. Nor would I have wanted my parents to have denied me the opportunity for life.

Understanding that the E4 allele is the original ancestral allele, I can't help but wonder if it confers some evolutionary advantage that we may not yet be aware of Among those of us living a Westernized lifestyle, I tend think that the only disadvantage we experience is that of a genetic/environmental mismatch. Rather than tinkering with the original APOE gene...shouldn't we instead be focusing on cleaning up our lifestyle? Thinking big picture; isn't our mismatch a good analogy for what we've done to the planet? Perhaps cleaning up that and our food supply, etc. might be a better path. Tinkering with evolution is a lot like playing with fire; could turn out OK, could be a disaster.

I DO like your Alzheimer's network diagrams, especially the second more expanded one. It beautifully demonstrates the myriad opportunities we have for working on optimal health to avoid this devastating disease. It also strongly supports a systems approach to preventing/treating the disease, like Dr. Bredesen is applying.

Lance, ANOTHER amazing thought-provoking post.

E4s seem to be different and to the point of many recent posts, some of us E4s respond in dramatically different ways to external, internal etc stimuli. Figuring all that out is becoming possible, but given our state of the "patient-doctor" relationship, I see no way this can be effectively scaled and implemented.

Agreed, with our current system; but did you see my recent post on P4 medicine? THAT gives me much hope. Dr. Hood has been approached by seven different countries, who are exploring implementation. He has backing from major philanthropists like Bill Gates, etc. It's happening, my friend...perhaps sooner than you'd think.

[LanceS]

Agreed, with our current system; but did you see my recent post on P4 medicine? THAT gives me much hope. Dr. Hood has been approached by seven different countries, who are exploring implementation. He has backing from major philanthropists like Bill Gates, etc. It's happening, my friend...perhaps sooner than you'd think.

Julie,
I saw it and think it could be a game changing investment. It doesn't make up for that operating system he made us all purchase but its a start ; )

Thanks for posting that, certainly something to watch for in the future.

Cheers (E4, appropriate of course)