Posts Tagged ‘ mutations ’

Genetically Engineered Babies: Good Or Bad Idea?

Wednesday, February 20th, 2013

Would you want the option of harnessing the power of genetics to alter the DNA of your unborn child? Would you want this to prevent disease? Select physical characteristics? Or “design” your baby by changing the genetic code? 

Such was the topic of an Intelligence Squared debate held in New York City on February 13. Two experts argued that genetic engineering should be banned; two experts argued that it should be supported. The audience – of which I was a part – had a chance to vote both before, and after, the arguments were made. Prior to the debate, I was in favor of supporting genetic engineering – with many caveats. After listening to both sides present their point of view, I pondered three points to help me come to a final decision:

Is genetic engineering feasible?

The science of genetics is fast paced. Although we don’t have much in the way of actual examples, it is worth assuming that it would be feasible at some point in the future. That said, my position is that it will only be worth considering for diseases or traits that are shaped by a single gene. There are certainly many diseases for which this is the case, such as cystic fibrosis and Huntington Disease. I certainly think there may come a time when it would be possible to try to intervene biologically to correct the mutations that underlie these conditions. However, bear in mind that most diseases and traits are believed to be due to the effects of many genes (polygenic) as well as environmental influences (multifactorial). Even height, which we think of as being “genetic”, is due to the combined effects of many genes as well as environment, and hence is multifactorial. Eye color is not as straightforward in terms of genetics as you might think. So … I think we can have the conversation about those more rare diseases and traits that are due to the “necessary and sufficient” effects of a single gene which can be identified along with the gene product. Having the debate about polygenic and multifactorial traits (more on this below) seems to be morphing into science fiction rather than science (unless science proves that wrong).

Why should we pursue it?

The primary reason would be to eradicate disease, especially disorders that are known to cause premature death. Certainly think about the life of a kid with cystic fibrosis – who wouldn’t want to spare a child that? Huntington Disease is an interesting example because it reveals that genes don’t just express themselves at birth – they can have a deleterious effect in adulthood. If we could alter that gene and prevent Huntington Disease, shouldn’t we do that? Some cases of breast cancer involve the primary (though not fully deterministic) effects of a single gene – again, if we could alter that mutation, wouldn’t we do that?

Why shouldn’t we pursue it?

Many feel that there are ethical considerations. For example, some do not like the idea of changing DNA – in essence, the thought is that it should be left alone. However, in terms of disease treatment, it’s worth noting that we do have examples of changing what a mutation does, and in the process keeping people healthy. A great example is a type of lymphoma caused by the “Philadelphia Chromosome” (so named because the mutation was discovered by scientists at the University of Pennsylvania). While the discovery was made in 1960, it took about 40 years to discover a genetically tailored drug that keeps the disease in check and allows people with this mutation to lead healthy lives. Although this isn’t genetic engineering in the strict sense, the principle is the same – alter the effects of DNA to change the likelihood of disease.

Less clarity surrounds the use of  genetic engineering to try to give parents the opportunity to control a variety of traits in their child to be – their appearance, personality, intelligence. As discussed by Melanie Abrahams, the pregnancy editor at Parents.com, the issue is would you want to create a Super Baby if you were given the choice? Again, my two cents to throw into this part of the debate is that it’s hard for me to imagine genetic engineering for polygenic, multifactorial traits – which includes appearance, personality, and intelligence. But then again, we don’t really know, do we?

Where do I land on this issue?

Bottom line, I support the idea of genetic engineering for well-defined diseases that are known to cause suffering and death. I don’t see any difference between designing a drug that is tailored to counter the biological effects of a mutation, and in principle directly altering the mutation. I don’t like the idea of applying genetic engineering principles to anything other than disease. Even “black or white” questions have their gray area.

DNA Structure via Shutterstock.com

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Dads, DNA, And Choices

Thursday, September 27th, 2012

The scientific paper describing the increases in DNA mutations that correspond to increases in paternal age – published last month (click here to see my discussion of the scientific aspects of the study) – has generated lots of discussion about the need for reconsidering how age may affect paternity and fathering. See, for example, Lisa Belkin’s thoughtful discussion about the utility of men hearing the ticking of a biological clock.

It can be argued that the biological role of fathers, with respect to age, has not received as much attention because we think of the biological clock as primarily representing the probability of being able to reproduce – with those effects being, of course, most pronounced for females. What is now emerging into the public awareness (based on a number of studies conducted over a number of years) is that paternal age – like maternal age – may be associated with an increased risk for passing on certain genetic risk factors that may confer risk for disorders.

We may get to a point where there are risk charts that quantify the increasing probability of paternal mutations that correspond to age and associations with risk for various disorders in offspring (much of the interest right now comes from the potential links between paternal age and autism). Consider, for example, this chart showing the increasing probability of having a child with Down syndrome as predicted by maternal age.

The complexity here is that prospective parents have to consider, in most cases, probabilities rather than certainties (unless there is a screening for a known genetic disorder that runs in a family). Is a 1% chance, versus a .5% or a .01% chance, enough to change someone’s family planning? This is tough to answer. For some people, it may be highly influential. For others, social and personal factors may override such probabilities. What is clear is that genomic research will continue to deliver more and more probabilities in the future (near and far) – and the information that is generated will pertain to both prospective moms and prospective dads. And that prospective parents will have to make more and more complicated choices that are partially (but not fully) informed by genomics.

Statistics and probability via Shutterstock.com

 

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Autism And Paternal Age: What’s The Take-Home Message For Parents?

Friday, August 31st, 2012

You may have read recently about a study that links the age of a father with the risk for autism. While there is some real science here to report, there is also the possibility of making too much of all this. So let’s break it down. 

Prior studies have suggested a link between the age of a dad and the risk for autism – as a dad’s age increases, so does the risk. The new study (published in the journal Nature) reports on a possible mechanism for this: it involves the number of genetic mutations that are passed on to a child. Click here to read a summary in the journal.

There are a few underlying ideas that are important. This line of research is showing that genetic mutations are much more frequent in a father’s sperm than in a mother’s egg. This makes sense, in that the sperm are produced throughout the lifespan in men, but women are born with their lifelong supply of egg cells. The authors of the Nature paper suggest that there is a steady increase across decades in a man’s life – so that when you are 40 you will produce more mutations than when you are 30 (and so on).

What’s the connection with autism? Well, right now it is a very indirect association. There is lots of interest in the idea that spontaneous mutations play a role in causing autism. Lots of papers have been published on this over the last few years. So the thinking here is something like connecting the dots – if spontaneous mutations are involved in the etiology of autism, and a dad’s age is a primary source of such mutations, then perhaps there is a link.

All that said, keep in mind the following:

1) The new study published in Nature did not provide any direct association between the mutations and autism

2) The assumption is that many of the mutations are harmless (and in fact somewhat normative)

3) There is, at this point, no clinical screening process to determine or suggest that a father passed on a mutation to a child

4) There are, at this point, no genetic counseling implications

Perhaps most importantly, there are lots of factors that contribute to the etiology of autism. There are certainly heritable factors that go beyond spontaneous mutations. And there are undoubtedly non-genetic factors as well.

So where are we at? At this point, spontaneous mutations are just more potential pieces of the puzzle with respect to the etiology of autism. They will continue to be researched and, hopefully, may in the future reveal more about the underlying biology of the disorder. But it’s way too early to begin to transfer the basic science into diagnostics and prevention – and too early to know what role spontaneous mutations will be shown to play in the broader context of multifactorial influences on autism.

DNA image via Shutterstock.com

 

 

 

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