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The V.
11-28-2001, 12:23 PM
Here's something I've been thinking about for some time, and would like to hear what people believe-- the human cloning thread made me think of this again.

One serious problem, which humanity has brought upon itself, is that we have removed ourselves from the natural cycle of selection, and thus we become a dysgenic population -- the quality of our gene pool, if you will, is dropping.

One example, one that we can already see quite clearly the effects of, is that we have removed the strong selection pressure for good eyesight. In nature, an animal which has poor eyesight is usually killed quicker than one with better eyesight, so on the whole, there is a relatively strong pressure to eliminate alleles (an allele = a possible form of a gene) which cause poor eyesight.

For millenia, humans have lived in communities, and, although those with lesser eyesight were not always treated as well as those with, the reproductive success of those with poor eyesight was not nearly as reduced as it would be in a natural environment. So, the selection which normally "purifies" the gene pool, by reducing the ability of undesirable alleles to reach future generations, has been removed.

In turn, there are a huge number of humans at the present who have myopia or other vision impairments. Nowadays, with corrective lenses, selection for good eyesight pretty much goes away altogether -- if individuals with the genes which cause myopia, et al, are not less successful at reproduction than those without, the allele(s) which cause myopia will not naturally be removed from the population.

This can also be applied to any other characteristics which we have removed the natural selection upon.

Given that we have significantly altered our species' natural ability to weed out "defective" alleles, do you think we should use our technology to replace this "purifying" behavior? By this, once we develop the ability to selectively genetically alter a living being (which will probably happen in our lifetimes), should we use this ability to correct defective alleles (like those which cause myopia) and reduce the prevalence of these alleles in the population?

If we should do this, should we also use this ability to improve the human race in general? I.e. make ourselves smarter, stronger, faster, etc.?

Series X4 1.0
11-28-2001, 12:44 PM
The natural selection will always be here with us. Our development, no matter where it goes, is just as natural as everything else. You still havn't realized that you're just trapped in a dark dying world.

I'm not against it, I don't support it. Because:

30% of you will die of cancer.

50% of mankind is starving.

People are raped, murdered, abused, commits suicide. There are wars, small ones in our daily lives, and big ones we can't experience for ourselves.

People continue to live because they can't see their life for what it is.

lightatdawn
11-28-2001, 02:39 PM
One serious problem, which humanity has brought upon itself, is that we have removed ourselves from the natural cycle of selection, and thus we become a dysgenic population -- the quality of our gene pool, if you will, is dropping.
This is a problem I have pondered over for hours with friends. The fact of the matter is, humans protect their weak and dying. In no other species (that I am aware of) do the strong keep the weak alive to allow their weaker genes to continue to the next generation.

Now I'm not suggesting that we shoot all our old, sick, handicapped, weak, and less intelligent people. The fact that we value all human life (some of us more than others it seems) is one of the things that has allowed us to get to the state that we are currently in. We band together.

Other animals adapt to their surroundings over time. Humans have yet to do so. We adapt our surroundings to ourselves. It's another thing that makes us different.

Some people say that cloning is unnatural. Or genetic engineering. But what is natural? Some animals use sticks and rocks in their hunt for food. e.g. Otters. So is that unatural? No. But it could be argued that sticks are found in nature... So we ask; Is a farmer using a machine to sow his fields unatural? No. Its just a more advanced rock. Built from things that naturally occur (or built from things built from things that naturally occur). My point is this: Who is to say what is natural and what is not? Some quickly lose sight of the fact that we too, are animals. And different animals have different tools, defences, and methods, to ensure their survival. Throughout our history our inventivness has been our method, and it has proven very effective.

If a young goldfish is placed in a large bowl it will grow large. Take another goldfish of the same age and type, and place it in a small bowl. It will not grow past a certain size. Whos to say cloning (for instance) isnt our method of dealing with a smaller bowl?

gnu-ehacks
11-28-2001, 09:23 PM
Series, I have a question. Do you believe that people who commit suicide are smart or stupid?

oskilian
11-28-2001, 11:18 PM
I'll just say this:

C'mon, we're evolving, so let's keep on evolving!!! I go with #1

Oskilian

Yoshi
11-28-2001, 11:21 PM
...we ar getting taller and taller, not smaller and smaller.
Sure, our brain is bigger than of our ancestors, but we used just 1/10 of it!. What is the point of building better human? What do you mean by "better"?
-------------
322reenignE

The V.
11-29-2001, 12:29 AM
We are taller, not because we've genetically changed, but because we are no longer stunted by malnutrition; more HGH (human growth hormone) is released when adequate food is ingested. This makes sense -- growth is a very costly thing, in terms of energy, both to grow, and to maintain the larger frame. If the food supply is scarce, the organism will have reduced growth.

There is also no evidence that we're smarter than we were 2,000 or more years ago. We have more technology, and more education, but it's likely that if you could take a baby from 3,000 years ago into the present, and raise them here, that they would be as mentally capable, on average, as anyone else.

By bettering, I mean that we could use the technology for a number of purposes to deliberately improve the function of the body. It's conceivable that we could improve many aspects of the human. For example, maybe it would be possible to alter genes involved in cardiovascular endothelial cells (the inner layer of the cells of the blood vessels) to prevent cholesterol accumulation, and decrease the risk of heart attacks. Alterations to the immune system could theoretically stop people from developing immune disorders, like juvenile onset diabetes, MS, allergies, etc.

Alterations to the shape of the human spine could reduce lower-back problems. Many get back problems because our spines are slightly off from optimal for bipedal creatures, which is good evidence that we evolved from quadrupeds. Now, evolution helped us along, but we aren't perfect -- being as most reproduction, historically, took place when our ancestors were 12-20 years old, we've developed a spine that will do very well -- for about 40 years, but after this time, people get spinal problems, simply as a result of the shape of our spines. Natural selection doesn't help to eliminate undesirable traits that don't alter reproductive success.

It would also be possible to give people "better genes" -- there are many genes that help to influence intelligence -- so you could, in theory, give a person a better chance of being a genius by altering their genetic makeup in the early embyronic stages.

doubleanti
11-29-2001, 12:36 AM
that was a really good post series... i couldn't have said it better...

hmm... speaking of natural selection and environmental differentiation over time... i believe my biology instructor pointed out that women, around about 20 or so, gain 15 pounds for childbirth purposes... and that in the past [millenium ago...] they lost it since their activity deemed it so... but that changed now... and that incoming college freshmen women get a 'freshmen-15'... she [my biology instructor] fortunately never got it... but perhaps we shouldn't hold back because our tweaking with human genetics is part and parcel of our evolutionary process and the masterplan of the future...

all the world's a stage...

rick barclay
11-29-2001, 07:35 AM
Your theory sounds good on paper v, but I see one flaw in it.
You're basing your cause and effect on a 100 percent success
rate, and if that were possible, then we'd all say yea, go ahead
with it. But total efficiency in genetic manipulation or technology
or whatever you want to call it is in my humble opinion totally
impossible. And once you have an incident where the guy with
the scissors or the test tube says Oops! Stuff happens, then the
world will be down on you like a pack of hungry flies. Your ideas
will be considered and discarded as just so much Orwellianism.

rick barclay

Camilo
11-29-2001, 07:49 AM
perhaps what we are doing is changing the method of the natural selection, who says that the one with a 'defective gene' also has the most valuable one and with reproduction he will 'purify' it and in the process the 'defective' is fixed?


Camilo

adrianxw
11-29-2001, 08:50 AM
Firstly, I am not quite sure what Camilo is saying here, but it is possible he is saying the same as me, if so, please excuse the plagiarism!

My point is that we got to where we are today by accumulating many small genetic modifications, and allowing the natural selection process to promote reproduction of those modifications that were effective survival strategies.

If a potentially advancing modification was detected in some form of screening, would it be recognised as advancing, or would it be edited out as an error?

I wonder if by following a "genetic error correction" policy, we might be resigning homo sapiens to an evolutionary dead end?

Justin W
11-29-2001, 11:17 AM
Humans are notorious for using new technology to their own ends. Genetic manipulation will be no different. Its goal will not be to better mankind's future, but its present. War is an obvious example. In WWII, Hitler began a program for genetic engineering given the technology of his time. Thousands of people were breed and raised by the state for the sole purpose of better cannon fodder. They were brain washed, and slaves.

I don't think any government today would/is not use this for a better, easier to control soldier. The private sector can come up with just as bad of scenarios in the name of science and profit. Billionaires raising clones of themselves and periodically slaughtering them to harvest organs that need to be of adult age.. perhaps entire bodies would be used and the brain discarded. If nothing else, a transfer of minds, even if through indoctrination and controlled experiences in their upbringing. The best thing going for the poor really, is that the rich eventually die and their children squander. What happens when the cruelest rich are the ones that live thousands of years? How much do they accumulate?

I know it sounds like sci/fi, but then again, so would cloning and genetic manipulation twenty years ago.

Basically, I don't trust humans to control human genetics. ;) If it isn't as dramatic as the stuff I've said, it will still be a form of discrimination. How many people that really made a good difference in the world would not have been if they were tinkered with? What would racisim do? Mixed with terrorism and gentic tinkering viruses? Big can of worms if you asked me.

The V.
11-29-2001, 12:26 PM
Originally posted by rick barclay
Your theory sounds good on paper v, but I see one flaw in it.
You're basing your cause and effect on a 100 percent success
rate, and if that were possible, then we'd all say yea, go ahead
with it. But total efficiency in genetic manipulation or technology
or whatever you want to call it is in my humble opinion totally
impossible. And once you have an incident where the guy with
the scissors or the test tube says Oops! Stuff happens, then the
world will be down on you like a pack of hungry flies. Your ideas
will be considered and discarded as just so much Orwellianism.

rick barclay

Of course you couldn't have 100% success in manipulating genes. You don't have 100% success in ANY kind of medical therapy -- does this mean therapy itself is not done?

To address adian's concern -- there is no INTELLIGENCE behind genetic purification by natural selection. Individuals with poorer alleles tend to reproduce less, on average, so the alleles become less common.

So long as new modifications didn't decrease the ability of the individual to reproduce, there's no reason natural selection would select against it.

Plus, the whole reason we'd do this is because NATURAL SELECTION ISN'T HAPPENING in humans. Blind people can live productive lives, and reproduce, instead of the case in all other species (which use vision) in which being blind is practically an instant death. People with sickle cell anemia, people with hemophilia, people with genetic predispositions from cancer are living long *and reproducing*, wheras in the wild, their reproductive chances would be significantly below average.

If natural selection still existed for these genes, there would be no need to replace it technologically. But for the past few thousand years, we have been eliminating more and more of the natural ability of the gene pool to weed out undesirable traits. Undesirable traits, like poor or no vision, predisposition to cancer, and various genetic defects are no longer being reduced in the population.

Because defects are no longer being reduced, and because there is always a slow introduction of genetic defects via mutation, the overall proportion of defective alleles to non-defective alleles will rise, and the gene pool will become more and more polluted.

As to what constitutes a defect: It's often quit obvious. If your hemoglobin molecules can't bind oxygen, or fail to bind adequate oxygen, it's a defect, not a feature. If several key DNA repair mechanisms no longer function (i.e. genetic predisposition to cancer) it's a defect. If the eye is malformed such that the muscles cannot properly deform the lens to an appropriate amount to focus light on the retina, it's a defect. If your lung tissue is unable to produce surfactant (necessary to reduce the amount of work it takes to breathe) it's a defect.

rick barclay
11-29-2001, 03:05 PM
>Of course you couldn't have 100% success in manipulating genes. You don't have 100% success in ANY kind of medical therapy -- does this mean therapy itself is not done? <

Ah, but we're not talking just any medical therapy here, my friend. We're talking cloning, genetics, and all it's associated
pitfalls. And the fact that you know a 100% success rate
cannot be maintained should also warn you of the consequences
that any failure of a Thalidomidic nature will be followed by a post-
thalidomidic response from the public and the media. We're not
talking prozac or cures for baldness here. The moral issues are
being discussed and debated world-wide, and it would not
surprise me in the least to see in the future some violent responses to stem cell research and cloning, same as we have seen in regard to birth control.

rick barclay

The V.
11-29-2001, 03:58 PM
Thalidomide was a very bad case of lack of sufficient testing to ensure safety. It is quite safe for any man, or any non-pregnant woman to take, and in fact, it is proving to be a very good drug to give cancer and HIV patients.

In any event, sooner or later, our species will need to address the issue of gene pollution. Either we need to resort to artificial selection (i.e. eugenics), which is incredibly unethical, or we need to modify genes.

Sooner or later, it won't become an option, it will become a necessity. The more defects we cure or treat, the more these defects will occur. And it will never get better unless there is some form of selection towards purifying the gene pool. Selection by differential reproductive success has been significantly reduced, in some cases almost to the point of being entirely absent. This leaves selection by controlled reproduction (i.e. everyone being told how many children they can have, and with whom) which has proven to be an adequate replacement for natural selection in animal breeding. Humans, however, may not like this much.

Artificial selection by genetic manipulation seems the only practical way to solve the problem. If the status quo is maintained, the gene pool will degrade, which could ultimately destroy the species as a whole.

doubleanti
11-29-2001, 04:39 PM
about 100 percent efficiency... i would imagine that since altering chromosomes is on a much smaller scope then something further involved in biology... that the efficiency would be much more stringently aligned... but until a maybe a week after we've reviewed genetics i wouldn't be more well read on the subject...

>is changing the method of the natural selection

that's my main concern when it comes to science 'playing god'... but again it could be all part and parcel... someone thought along the lines of 'if god wanted us to believe in god, s/he would not have allowed us to think otherwise'... and in this sense, it applies...

rick barclay
11-29-2001, 04:51 PM
>Thalidomide was a very bad case of lack of sufficient testing to ensure safety. It is quite safe for any man, or any non-pregnant woman to take, and in fact, it is proving to be a very good drug to give cancer and HIV patients.<

How in the world did we get from being a pregnancy aid to
cancer and HIV treatment? I wasn't aware that thalidomide was
even in use anymore.

And I don't think you're going to have much success convincing
common folks that their genes are polluted. "Whatchoomean
my gene's polluted, Willis?"

Or is this where the Genome Project is leading us? It seems to
me a lot of gynocologists will be doing things to prospective
moms in the name of "science" without telling the moms just
what it is they're doing. Because, I imagine, if they do start
telling those mom-to-be what they have a mind to do, then the
mothers will turn and run screaming from the doctor's office.

You can't just go and start operating on people's genes without
telling them about it, and once they do know what you're up to,
all hell is going to break loose. And another scenario might be this: my late brother-in-law was a congenital cancer risk. Say
his wife tells her gyno and the gyno assures her that a gene
alteration will eliminate any chance of her child being a cancer
risk. But after the gene alteration and the child is born, it turns
out the child is myopic and retarded. What then? Is the doctor
responsible? You'll have a hard time convincing anyone otherwise.
I think before the general population is ready to accept any kind
of gene therapy on itself, there will have to be at the very least a 99% success rate on gene research in laboratory testing. And
even that might not be good enough, because the moral issues
here are clearcut and sharply divisive.

rick barclay

The V.
11-29-2001, 05:03 PM
Thalidomide has a LOT of good properties. It reduces nausea, which was why it was given (unfortunately) to pregnant women.

It is also an antiangiogenisis agent; it reduces the body's ability to form new blood vessels. Because cancerous tumors require a large amount of blood, they can often be destroyed by literally starving the cells, by preventing the body from creating new capillaries to feed the new cells.

I am not sure exactly what its application was in HIV/AIDS; it may have been used simply to treat symptoms.

I do know there are reasons to use thalidomide in treatment of leprosy, AIDS, and cancer.

If we can get gene targetting down to an exact science, I think a lot of people would accept minimal risk to prevent problems. For example, if you knew your child would either have a 65% risk of cancer (as you would have if you had a certain mutation), or a 0.1% risk of developing complications, which would you choose? People vaccinate their children for many things, and that poses a risk of death, in extreme cases. This "gene vaccination" would be no different. Eliminate diseases before they become too complicated to treat.

doubleanti
11-29-2001, 05:08 PM
i gave blood today... i was pretty scared, it was a bit painful... the needle was deep... i bring this up because consent changes as the winds and, even though you know you'll be fine anyway, you still get the butterflies.... [i did at least...] so to what extent does emotion and rationalization conflict about a matter like this? or anything? that's it's own topic...

different strokes was a good show...

rick barclay
11-29-2001, 09:01 PM
In my sister's case, she chose not to have children--a very wise,
no-brainer of a choice. Her husband died of brain cancer after a
very, very long illness, during which I realize now that there was
a lot of denial and concealing on both my sister's and her husband's part. He had a master's degree from Seton Hall U.
and was personnel manager at Alcan Aluminum and in the prime of his life when the first symptoms struck--fainting spells. He lost
his job and his ability to work several years later, and by the
time he died he needed constant attention and monitoring. I never met anyone like him. To this this day I think of him as the
happiest man alive, because that's how I remember him before
the cancer took over. He was emminently intelligent, treated
his unworthy brother-in-law like a blood brother, and was just
the most decent man one could imagine. But cancer took him.
My sister knew the risks of having children by this man. What do
you think her decision would have been had a genome process
been available to her? She's every bit as intelligent and educated as her husband was, very confident in the correctness of her decisions. Yet knowing my sister as I do, I don't think she would have risked having a child even if the percentages of inheriting
that mutant gene were less than .0001%. I don't think she would
have had the baby. We men can sit here all day long at our computers and debate the merits of risking our children's health,
but it's the women who have to make the ultimate decision in
matters involving birth defects and taking risks, and they're the ones who bear ultimate responsibility for whether or not their babies are born as functional human beings or human vegetables.
Every married man here on this board who has an opinion about this topic should stop and ask himself, "How would my wife and I deal with this. Birth defects run in my family's history. What do I
tell her? Should we go through with it and let the scientists alter
our dna or whatever it is they do to change the gene structure and have a natural child? What if she says, 'No?' What if she says
'Yes?'" There's a thousand questions to be answered, here, a thousand questions before even the first step is taken. And after that first step there's more questions and more doubt about
this being the right decision, right up to and after the child is born. And should that child be born deformed in any way, what
then? At whose urging did we do this to our baby?
And so on and so forth. This may seem like an easy topic to debate, scientifically, but there are personal considerations that have to be taken into account, too, and that's what is going to make the subject of genetiacally altered babies a most controverial point of contention in the future.

rick barclay

Justin W
11-29-2001, 09:35 PM
I agree, it is not likely to take hold in the average person's life. Not unless some pretty unethical scare tactics take place, and then like Rick says, what if there is something wrong after the alteration?

Gatica was a good movie, anyone here see it? Discrimination has enough of a presence in our society, why add genetic manipulation (again as in WWII and the "master race")?

EDIT: I am not convinced the gene pool is going to hell in a hand basket. Believe it or not, people with handycaps are still at a considerable disadvantage (not that many/most of them don't have great genes anyway). Last I read, the average life span for a blind person in the US was 9 years of age. I think there is a huge human population on Earth, and disease is just a symptom of that (and NASA dumping radioactive waste on us from burned up satellites, of course..)

The V.
11-29-2001, 10:10 PM
The overpopulation and the selection are parts of the smae problem.

In many species, less than one in three individuals reproduces, period. So only those with the best complement of genes stand much of a chance. This rapidly purifies the gene pool.

I never said that selection, as a whole, is completely gone. It will always exist in SOME form. But, the issue is that it is highly reduced. In its current state, it is weeding out defects slower than defects emerge.

As I said, we *already see this*. No other species which relies on eyesight has the degree of prevalence of eye malformation as the human. It's not a theory that the gene poll *may become* polluted, it's a fact that the gene pool *is* polluted.

Another interesting point: Allergies. In countries with poor health care (3rd world countries) there are populations that have not felt nearly so much of this effect as the 1st world countries. In many of these populations, there ARE no individuals with allergies; they're incredibly rare. Yet the vast majority of Americans DO have allergies -- one of the least harmful autoimmune disorders, but it may be a distrubing sign. Nobody knows what the exact link between developed nations and allergies is, so it can't be necessarily blamed on gene pool corruption, but that is one suspect.

And BTW: To Rick: 0.001% chance of getting a gene which promotes cancer would be better odds than most children have -- cancer is actually quite common. In fact, every human, if they live long enough, will develop cancer at some point; those who don't develop cancer just died of something else before they got cancer.

Cancer is not even necessarily genetic in nature -- you'd need to test the gametes for corrupt copies of certain genes (the oncogenes). But it's more than possible for someone to just get unlucky -- have all the right genes to give them good chances of surviving cancer, yet not develop it. Having bad copies of genes which relate to DNA repair just increases the risk of cell mutation, and thus cancer -- the risk of cancer is always present in any human.

Also, to those against gene therapy: would you withhold a cure for a disease from those who can use it? I'm not necessarily talking about artificial reproduction -- but if you could genetically sample your child, either in utero or after birth, wouldn't you opt to correct genetic flaws? If you knew you could reduce your child's risk of cancer from 50% to 1%, would you? Obviously, after birth, not all genetic flaws could be corrected, but many could.

Justin W
11-29-2001, 11:33 PM
I'm not necessarily talking about artificial reproduction -- but if you could genetically sample your child, either in utero or after birth, wouldn't you opt to correct genetic flaws?

Predisposition to disease is debatable. Some things you catch or develop from your environment. Most things. Our environment and the fact we don't kill anyone "defective" is the reason we have more sick than the animal kingdom on average. I for one, don't believe something just because it is a prevalent theory. We should all question these ideas. New != better. Nor do I believe the current methods we use to determine what genes do is foolproof or even very good. I will let my child develop naturally as MY child, not something I point and click into existence. Maybe I don't like a certain color tone? Maybe my child misses something really important in life because of this. It is my fault, not chance. Maybe my child is destined to be deaf and this is very hard on him/her. But maybe he/she needs this to become the next Beethoven. If I didn't want a child that was a part of me, I would adopt (which is a better option than genetic engineering, and often better than having your own kids).

Justin W
11-29-2001, 11:35 PM
What about discrimination and technological abuse? These issues have not been addressed.

rick barclay
11-30-2001, 12:37 AM
>Another interesting point: Allergies. In countries with poor health care (3rd world countries) there are populations that have not felt nearly so much of this effect as the 1st world countries. In many of these populations, there ARE no individuals with allergies; they're incredibly rare. Yet the vast majority of Americans DO have allergies -- one of the least harmful autoimmune disorders, but it may be a distrubing sign. Nobody knows what the exact link between developed nations and allergies is, so it can't be necessarily blamed on gene pool corruption, but that is one suspect. <

I think Americans are way too antiseptic for their own good. Their
battle against germs and dirt reach the fetish point for some. And
yet, as your studies reveal, the ambivalent reality in just such
cases where one's fear of things unclean touches upon phobia, truth would seem to indicate that it's more healthy to be a little more dirty than clean! But then again the dirt one encounters in
a Third World country is stretching that premise just a mite too
thin. But if you travel back in the opposite direction to squeaky-clean America you do find the daunting realization that too clean
might be just as detrimental to your health as African ebola. I think the answer lies somewhere in the middle of those two
extremes. You need just so much dirt as can safely distract whatever might ail you--just don't overdo it and give those bad
boys a good reason to fall in love with your body.

As to your views on cancer, yeah it will get you in the end one
way or another whether or not it runs in your family. Think how long a healthy man would live if he could live without that fear
of cancer. Some of the oldsters in Russia and its former republics
live to 130. Is it cancer that takes them in the end?
My father at 73 was at the peak of health for a man his age when one day while having his car fixed something, a stray piece of
debris flew into his eye. It was just a speck, but it irritated him
to the point where his eye became infected, and from that point on he deteriorated until it was discovered that he had cancer.
The cancer was found in the area of his infected eye and he died at age 76. If he hadn't been in that garage at the appointed time, who knows how long he would have lived.
But my brother-in-laws case offers strong testimony that there
are genetic forms of cancer, too. He knew it ran in his family's
history. There was no untimely event that set it off; it was there all along in his brain, just as it was in prior generations, planted
there like a seed and set to germinate at a proper time. Who
knows? Maybe no amount of gene correction could have saved him. And quite possibly no amount of gene doctoring could have
saved his unborn baby. That could be another terrible truth we
have yet to discover as we travel into the wondersome world of genetics.

rick barclay

novacain
11-30-2001, 03:38 AM
I think the biggest change in our 'evolution' is that before most of the forces powering the change were external to the population ie nature, predation.
Now they are internal ie disease, fashion (eg Japan's population is getting more 'western' due to the 'hollywood' influence). This is due to our larger population size and density.

adrianxw
11-30-2001, 04:57 AM
Sorry, I know this is going back a bit in the thread, but Thalidomide exists in 2 forms. They have the same formula but have what is called a chiral centre, the two forms are, simplistically, left handed and right handed. Such forms are called enantiomorphs. One enantiomorph is used now in a variety of cases as discussed, it was the other that was responsible for the disaster. The enantiomorphic selection process has improved dramatically since the 50-60's as has the understanding of such matters.

rick barclay
11-30-2001, 06:27 AM
Two days ago, I think I would have punched anyone in the nose
who told me they were going to treat me with thalidomide. Then
I would have run out of that doctor's office and up to the nearest
policeman and told him there was a man impersonating a doctor
who was trying to kill me.

But I'm a very wishy-washy type. My mind is easily changed. I
find it incredible that anyone who is familiar with the thalidomide
disaster of the 60's would trust anybody to use it on him in a
therapeutic way.

rick barclay

Scourfish
11-30-2001, 04:18 PM
Instead of creating new humans, we should work on bringing the dead back to life and use them to squash our foes, just like in the movie "Universal Soldier"

The V.
11-30-2001, 05:18 PM
Originally posted by adrianxw
Sorry, I know this is going back a bit in the thread, but Thalidomide exists in 2 forms. They have the same formula but have what is called a chiral centre, the two forms are, simplistically, left handed and right handed. Such forms are called enantiomorphs. One enantiomorph is used now in a variety of cases as discussed, it was the other that was responsible for the disaster. The enantiomorphic selection process has improved dramatically since the 50-60's as has the understanding of such matters.

Actually, thalidomide still cannot be used on pregnant females, because as it moves through the bloodstream, it racemizes (it converts to equal amounts of each form). So, in the blood, even if you injected people with only the R (+) form of the enantiomer, which is the medicinal form, it would equilibrate to 50% each of the R (+) and S (-) forms in the blood; when a chemical equilibrates to equal amounts of both forms, the mixture is called a racemate.

However, thalidomide is a teratogen (chemical which causes embryological defects), not a carcinogen. The S (-) form of thalidomide causes birth defects in a child if given to the mother during a specific time in pregnancy. It is completely harmless to an adult, in fact, it has no known side effects. Any male could take thalidomide with complete confidence; any female who is guaranteed to not be pregnant may also take it, and neither will experience anything undesirable.

Thalidomide will still never see use in pregnant women, because even though you can use techniques to isolate one form in the lab, in blood conditions, the temperature and pH are such that the two forms can freely convert between each other, and regardless of the initial proportion of R to S enantiomers, the drug will reach 50% of each form (a racemate) much faster than it will be removed from the bloodstream.

BTW, thalidomide is used in HIV patients because it also acts to inhibit the release of TNF-alpha. TNF-alpha is a chemical released into the blood during infection, which can reach very high levels in AIDS victims. This is undesirable because high TNF-alpha levels increase HIV activity; thalidomide can reduce the rate of HIV production, and help in slowing the progression of AIDS.

Thalidomide was a very unfortunate story. It's a very useful drug, and all tests, which had been conducted on animals and humans, showed no side effects. But the drug manufacturers failed to test the drug for teratogenic properties -- all the tests were on nonpregnant adults, so the terrible side effects which happen when given to pregnant women were unforseen. It is a horrific oversight, which has had a huge impact on drug regulations in many countries, and has changed how the drug industry and the governments of the world approach testing.

rick barclay
11-30-2001, 06:28 PM
Guess I owe that doctor an apology. :)

rick barclay

Oh, and btw, he WASN'T treating me for HIV.

adrianxw
12-01-2001, 02:33 PM
The V:

>>>
the R (+) form of the enantiomer, which is the medicinal form, it would equilibrate to 50% each of the R (+) and S (-) forms in the blood
<<<

So you are saying here that the enantiomorphs can exchange their chirality? That, frankly, suprises me, and interests me enormously. Do you have a url where I can read more on this?

The V.
12-01-2001, 03:48 PM
MANY enantiomer pairs exhibit this.

In thalidomide, it happens because one of the 4 components of the chiral carbon is a hydrogen atom. Further, because the chiral carbon is adjacent (alpha) to a ketone group, this hydrogen is somewhat acidic. In other words, the anion is stabilized by a resonance structure in which the negative charge is on the oxygen atom of the ketone. Oxygen, being an electronegative atom, accepts a negative charge better than carbon; this resonance structure makes the alpha hydrogen much more acidic than it would otherwise be, acidic enough that the molecule can dissociate into H+ and a carbanion without the presence of a strong base. This is true of any hydrogen alpha to a carbonyl group, in fact.

When it dissociates, the carbon changes from an sp3 hybridized carbon to an sp2 hybridized carbanion (the nonbonded electrons now occupy a p-orbital). The chirality is lost -- the geometry of this carbon is now trigonal-planar, not tetrahedral. It will quickly pick up a hydrogen again (it's acidic enough to lose this hydrogen, but not acidic enough to remain in this state for very long, except in a moderate to strong basic solution). When it picks the hydrogen up again, the hydrogen has equal chance of "attacking" the carbanion at either face; thus there is a 50% chance that the carbon will assume the R configuration, and 50% that it will become S. Over time, this dissociation and recombination will cause the enantiomers to equilibrate as the racemate.

Racemization is very common in chiral molecules where one of the 4 substituants is hydrogen, and the hydrogen is acidic because of neighboring atoms. There are other means of racemization, but all of them generally follow the same idea: they convert a chiral atom into one which is not chiral by altering the bonds to that atom. When the reaction is reversed, there is equal chance of creating either enantiomer.

The V.
12-01-2001, 04:33 PM
BTW, this is the reaction that racemizes thalidomide. Stereochemistry at the chiral carbon is shown, as are both relevant resonance forms of the planar intermediate.

Sorry for the crummy quality, I don't have a good organic formula package anymore, so i borrowed and modified an image I found.

Also (although my organic prof would've marked it off) I only included the unpaired electrons that we care about -- obviously, each oxygen should have 2 more pairs of electrons, and the nitrogens should have one more pair.

GaPe
12-02-2001, 07:07 AM
I think that human gene manipulation is good for us (people), beacuse we can become better humans.

novacain
12-04-2001, 08:46 PM
Regardless of our current ability to modify embryos it will soon be an available service.
Over 40% of parents said they would use the service to increase their child's IQ or to remove disabilities.
These kinds of percentages are a green light as far as marketing is concerned.
As we all know the world is driven by the dollar, not by morals, and there are big bucks to be made here.

Yoshi
12-04-2001, 10:57 PM
That's why people are getting greedier and greedier so worse and worse.
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322reenignE

adrianxw
12-05-2001, 04:14 AM
The V.:

Thanks for your explanation and graphic. I am currently sitting at my desk looking at the structural formula of Meclizine and wondering about the chiral centre there. One component is H, and there is an adjacent piperazine group which, presumably could lead to the same effect you described, (and described well I might add).

Yoshi
12-05-2001, 09:57 AM
Genetic manipulation of humans for unpractical purposes!
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Engineer223