DNA (2003) PBS

Episode 5: Pandora's Box

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Episode 5: Pandora's Box

We asked Jim Watson to give us a tour of the future. He believes DNA science should be used to change the human race. His views are both extraordinary and extremely controversial. Watson argues for a new kind of eugenics -- where parents are allowed to choose the DNA of their children -- to make them healthier, more intelligent, even better looking. His vision may be disagreeable, yet it's a natural consequence of the decades of scientific exploration launched by his and Francis Crick's discovery of the double helix. It's worth considering what effect the advancements in genetic science may have on our future.

Produced/directed by David Glover and edited by Joe Bini.

Beyond DNA: Genetics of the Future, by Magdalena Eriksson

The result of the Human Genome Project -- the complete sequence of human DNA -- presented several surprises, some of which seemed almost contradictory to long-held beliefs about how our genes work.

The total number of genes, estimated to be about 150,000 only a year before the sequence was completed, is actually only around 30,000, which may at first seem surprisingly small considering the complexity and sophistication of human beings. After all, our genes not only contain the blueprints for building every tissue in the human body, they also describe how to run and maintain the whole organism, control its development, and stably operate the activities of the brain -- all with a margin that allows for evolutionary experiments.

Interestingly, the sequence of the mouse genome, reported in December of 2002, showed an astonishing similarity to ours: 99 percent of the nearly 30,000 genes in a mouse have direct counterparts in man. Yet, we can easily point at several obvious differences between these species: we walk on two legs, mice on four; we can live for 100 years, mice rarely longer than a couple; we talk and play the piano, mice squeak and lack dexterity; and, perhaps most importantly, we think we're a lot smarter than mice.

Since the sets of genes in mice and men don't differ that much, the unique features of each organism must depend greatly on how our genes are used. The genes in a mouse follow a different program than the genes in a person. Scientists have recently started to realize the complexity of gene regulation -- how genes become active or inactive at different times during development and later in life. We have long known that proteins bind to DNA and recruit the transcription machinery that initiates expression of a certain gene or, alternately, that proteins may block a gene from transcription. In addition to that, a number of previously unknown ways to control gene expression have emerged in the last few years, some of which depend on parts of the genome that don't encode proteins.

Our genes occupy only about two percent of the human genome. The role of the rest, the so-called "junk" DNA, was long a matter of speculation. The completed sequence has allowed scientists to pull back and consider these huge expanses of DNA "nonsense" from a distance, one chromosome at a time. In the last few years, scientists have noted important functions for these non-coding sequences.

Comparisons of mammalian genomes have shown that certain tracts of the "junk" show a high degree of similarity among various species. This means that these conserved tracts are actually remnants of primordial DNA that have remained the same for 300 million years as mammals have evolved in different directions, which also suggests that they provide indispensable functions. The number of such non-coding regions of DNA has been estimated to exceed the number of protein-coding sequences. The search to explain the role of conserved non-coding DNA will likely occupy researchers for years to come.

Some stretches of DNA are necessary for correct packing of the enormously long molecules into compact, well-ordered chromosomes. When resting, DNA is coiled around protein complexes like thread on spools, making two turns around each spool of proteins. Little chemical markers lock the DNA to these spools. If these markers disappear, the genes they normally hold in place are taken out of storage and become available to enzymes that can read their code and use them for protein production. This lost marker function can be passed from one generation to the next, thus showing how our genome can carry inheritable traits that don't require a change in the DNA sequence. This phenomenon is called epigenetics.

Epigenetics suggests how evolution may be sped up. Minor or temporary changes in lifestyle or environment that occur before or during reproduction can cause visible changes in the next generation. Epigenetic changes may serve to allow us to respond swiftly to altered environmental conditions. Darwinian evolution, which involves long-term changes in the genome's DNA sequence, operates on a much slower timescale.

Another recently discovered genetic regulation involves non-coding stretches of the genome. These stretches turn into powerful tools when translated to RNA. Nature has invented its own remarkable strategy of silencing genes so that their information is hidden from enzymes, a stratagem called RNA interference (RNAi). Short pieces of double-stranded RNA dock at matching sequences of messenger RNA where they attract a protein complex, which efficiently breaks up the coding sequence and prevents protein from being created. This sort of control over when to turn on and off different genes is the basis of development; the right type of tissue has to grow at the right time.

Scientists have learned how to use RNAi in the laboratory, and the technique has become a popular research tool. It is possible to insert tailor-made pieces of RNA into cells. When these bits of RNA find their target in the genome, that part will be shut down. Researchers can then establish what effects the RNAi and the shut-down gene have by examining changes in the cells. Scientists are already exploring the use of this RNAi technique for medical purposes, including the study of various cancers and viruses, as well as HIV and the malaria parasite. It may also be used in combination with gene therapy.

Our understanding of how DNA runs the human anatomy is still fragmented -- we understand certain processes and principles in great detail, whereas others are still unclear. Some remain unknown. It seems the more we learn, the more we realize how much is left to explore.

Source: PBS

Documentary Description

A half-century ago, two unknown scientists heralded the dawning of a new era in biology and human life as they entered an English pub! Of course, Jim Watson and Francis Crick were hardly exaggerating. Their achievements almost single-handedly launched the new science of DNA. Interviews with renowned scientists and stunningly realized animations and reconstructions of key experiments offer an unprecedented glimpse of the molecular basis of life.


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