How biology’s most breakthrough led to anticlimax and arrests

When President Bill Clinton went to a White House desk 20 years ago to announce the completion of the human genome series, he praised the breakthrough as ‘the most important, most amazing map ever produced by mankind’. The scientific achievement is equivalent to the lunar landings.

It was hoped that within 20 years, our access to the range would change our understanding of human diseases, leading to better treatment, detection and prevention. The famous journal article that shared our genetic ingredients with the world, published in February 2001, was welcomed as a ‘Book of Life’ that could revolutionize medicine by showing which of our genes to which diseases led.

But in the two decades since, the series has been submissive. The potential of our newfound genetic self-knowledge has not been realized. Instead, there is a new frontier in genetic research: new questions that a new group of researchers can answer.

Today, the gaps between our genes and the links that guide genetic activity emerge as powerful determinants of how we look and how we get sick – perhaps we decide up to 90% of what makes us different. Understanding this ‘genetically dark matter’, using the knowledge provided by the human genome sequence, will help us to move further into the genetic secrets of our species.

Unraveled code

The cracking of the human genetic code took 13 years, US $ 2.7 billion (£ 1.9 billion) and hundreds of scientists looked through more than 3 billion base pairs in our DNA. Once our genetic data was mapped, it helped projects such as the Cancer Dependency Map and the Genome Wide Association Studies better understand the diseases that plague people.

But some results were disappointing. In 2000, when it became clear that the genome sequence was imminent, the genomic community excitedly began placing bets to predict how many genes the human genome would contain. Some bets were as high as 300,000, others as low as 40,000. For your context, the onion genome contains 60,000 genes.

Disturbingly, our genome contains about the same number of genes as a mouse or a fruit fly (about 21,000), and three times less than an onion. Few people would argue that humans are three times less complex than an onion. Instead, this discovery suggested that the number of genes in our genome has little to do with our complexity or our difference from other species, as previously assumed.

Great responsibility

Access to the human genome sequence also posed to the scientific community a number of important ethical questions, which were underlined by Prime Minister Tony Blair in 2000 when he warned: “With the power of this discovery comes the responsibility to use it wisely. “

Ethicists were particularly concerned about questions about ‘genetic discrimination’, such as whether our genes could be used against us as evidence in a court of law, or as a basis for exclusion: a new kind of twisted hierarchy determined by our biology.

Some of these concerns have been addressed by legislation against genetic discrimination, such as the 2008 U.S. Genetic Non-Discrimination Act. Other problems, such as the so-called “designer babies”, are still being tested today.

In 2018, human embryos were edited by a Chinese scientist, using a method called CRISPR, which makes it possible to cut off targeted parts of DNA and replace them with others. The scientist in question was then sent to prison, indicating that there is little appetite for human genetic experimentation.

On the other hand, denial of available genetic treatments to willing patients can one day be considered unethical – just as some countries have chosen to legalize euthanasia on ethical grounds. There are still questions about how humanity should handle its genetic data.

Disorders of diseases

Since the editing of human genes is still very controversial, researchers have rather investigated which genes are responsible for mankind’s diseases. When scientists investigated which genes were linked to human diseases, they were surprised. After comparing large samples of human DNA to determine if certain genes led to certain diseases, they found that many unexpected parts of the genome were involved in the development of human diseases.

The genome contains two sections: the coding genome and the non-coding genome. The coding genome represents only 1.7% of our DNA, but is responsible for the coding of the proteins that are the essential building blocks of life. Genes are defined by their ability to encode proteins: 1.7% of our genome is made up of genes.

The non-coding genome, which makes up the remaining 98.3% of our DNA, does not encode proteins. This largely unknown part of the genome was formerly termed ‘junk DNA’, previously considered useless. It contains no protein-creating genes, so it has been assumed that the non-coding genome has little to do with the things of life.

Surprisingly, scientists have found that the non-coding genome was actually responsible for the majority of information that influences the development of diseases in humans. Such findings have made it clear that the non-coding genome is actually much more important than previously thought.

Improved capabilities

Within this non-coding part of the genome, researchers subsequently found short regions of DNA, called enhancers,: gene switches that turn genes on and off in different tissues at different times. They found that enhancers needed to form the embryo changed very little during evolution, suggesting that it is an important and vital source of genetic information.

These studies inspired one of us, Alasdair, to investigate the possible role of enhancers in behaviors such as alcohol intake, anxiety, and fat intake. By comparing the genomes of mice, birds and humans, we have identified an amplifier that has changed relatively over 350 million years – suggesting that it is important for the survival of species.

When we used CRISPR genome care to remove this reinforcement from the mouse genome, those mice ate less fat, drank less alcohol, and showed reduced anxiety. While this may all sound like positive changes, it is likely that these enhancers have evolved in calorie-poor environments full of predators and threats. At the time, it would have been the key to survival to eat high-calorie foods such as fat and fermented fruits, and to be vigilant against predators. In modern society, however, the same behavior can now contribute to obesity, alcohol abuse and chronic anxiety.

Remarkably, subsequent genetic analysis of a large group of people in the population showed that changes in the same human enhancer were also associated with differences in alcohol intake and mood. These studies show that enhancers are not only important for normal physiology and health, but that changing them can lead to behavioral changes that have the greatest impact on human health.

Given these new research paths, it appears that we are at a crossroads in genetic biology. The importance of gene enhancers in health and disease is uncomfortably related to our relative inability to identify and understand them.

To make the best use of the sequence of the human genome two decades ago, it is therefore clear that research now needs to look beyond the 1.7% of the genome that encodes proteins. When investigating uncharted genetic areas, such as those suggested by enhancers, biology could potentially detect the next series of breakthroughs in healthcare.

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