Why sequencing the first human genome 20 years ago was so important

By Dr Jane Sarginson, Lecturer in Genetics

In the last few decades we have gone from celebrating the sequencing of the first human genome by the Human Genome Project to seeing the completion of projects such as Genomics England’s 100,000 Genome Project in 2018 and using genomic sequencing to help us diagnose, study and eventually treat genetic disorders.

A genome contains all the instructions needed to build and maintain the organism it belongs too.

The information is coded into our DNA, which can be read using sequencing, so in basic terms the Human Genome Project produced the first ever copy of our complete instruction manual.

Personally I’ve gone from being an undergraduate placement student working on a very tiny part of the Human Genome Project to being a genetics lecturer trying to persuade undergraduates that something that can be done in a few days by a machine that sits in the corner of the lab, at a cost of not much more than they pay for a month’s rent per genome sequenced, once required dozens of research groups from across the world to work together, took 13 years, and cost the equivalent of £2.18bn.

When I tell them that this was actually under budget and that the project was completed two years early, the real scepticism sets in and I generally start feeling like a bit of a dinosaur.

I generally don’t mention that the way I learned to sequence DNA involved creating radioactive pieces of DNA and reading the DNA sequence off an X-ray film with the help of a ruler.

The Human Genome Project was far more advanced than this but still involved rooms full of sequencing machines that did the job that a single machine can do now.

The Human Genome Project also contributed to the development of new sequencing technologies that have made large-scale sequencing of a patient’s genome a viable diagnostics, all of which is contributing to the development of new treatment options for genetic disorders

Genetics’ monumental changes

The field of genetics has changed faster than I could have ever imagined when I sat down in my first genetics lecture in the mid-90s and one of the biggest reasons for these rapid changes happened 20 years ago this week.

On June 26 2000, two very different men stood side by side at the White House with the then President Bill Clinton and the then British Prime Minister Tony Blair to announce the completion of the first draft - and this was very much a draft - of the human genome.

The two men were Francis Collins, the head of the international research collaboration known as the Human Genome Project, and Craig Venter, an American biotechnologist and businessman whose company Celera Genomics was also sequencing the human genome.

Venter had joined the race to sequence the human genome late, around eight years after the start of the Human Genome Project, but sequencing technology had moved on so much by then that Celera’s project caught up fast and in the end the heads of the two projects agreed to make a joint announcement.

It is fair to say, though, that these two men had differing views on how this draft of the human genome should be used and who should benefit from it.

Not unexpectedly, Collins supported the open access policy that the Human Genome Project was founded upon and Venter supported the commercialisation of this new resource.

This lead to debates about what genetic information could be used for and by whom, a discussion that spilled over from scientific conferences and company boardrooms to the House of Commons in the UK and the White House in the United States as people started to realise how important genetic information could be to understanding human health and disease.

Questions about use and ethics

There were questions not only about whether or not genes could be patented, but how an individual’s genetic information could be used.

For example in the future,would insurance companies be allowed to decide whether or not to insure you, or calculate your premiums, based on genetic risk factors?

Fortunately gene patenting didn’t happen and the human genomic sequence produced by the project remains a freely available resource that thousands of scientist continue to use every day.

The Human Genome Project formally started in 1990 after a great deal of campaigning by people such as James Watson, who was one of the scientists awarded a Nobel prize for discovering the structure of DNA and the head of the project until 1992.

At the time, many people wondered what use having a copy of the human genome would actually be, apart from keeping a bunch of scientist occupied for the next decade or so, especially at a cost of an estimated £2.4bn.

They were also quite skeptical about whether or not they would even be able to do it because it wasn’t an easy or straightforward task.

When the first draft of the human genome was announced on June 26 2000, it was actually only 90 per cent complete and still needed additional work before it was of good enough quality to use for research. It took until 2003 to get this to 99.9 per cent.

The version that I currently use with my students was finalised in December 2013.

It was a big task and not one that finished when the sequence was completed.

Incredible insight from our genetic code

The first copy of the human genome became the framework we hung all sorts of other information off, as we identified new genes and the sections of DNA that helped regulate them, but one genome wasn’t enough.

Understanding how the tiny differences in our genetic code help make us all so individual can give incredible insights into our shared biology and history, and perhaps more importantly from a medical prospective identifying what genetic differences contributed to human disease.

On the very simple principle that knowing what is broken is the first step to fixing it.

Genetics has contributed to the targeted treatment of a wide range disorders, particularly cancers.

My own research interests are in pharmacogenomics, which focuses on using genetic information to help select the right drug for individuals, at the right time and at the right dose. 

I hope anyone who has ever had to go back to the doctors because a drug hasn’t worked for them or because they are having side effects would agree that this is important.

Bringing new breakthroughs

One of my main research focuses at the moment is treatments for depression, where early and effective treatment can have a big impact on the patient’s life, but they may currently have to go through several different antidepressants at different doses before they find one that works for them.

We still have a long way to go with this but each year brings new breakthroughs. 

If you visit one of the websites that were originally set up to share the information produced by the Human Genome Project today, you’ll be able to access information on genes, gene regulation, genetic variation, including linked clinical information.

You can compare a human gene with its equivalent across a whole host of species and much more.

Freely available to researchers

More importantly all this information is still freely available to whoever is interested, which researchers all around the world contributing more information all the time.

There are also data bases available to researchers of genomic sequences contributed by individuals with different characteristics, including specific diseases.

Genomics England’s 100,000 Genomes Project is an independent UK based project focused on patients with a rare disease and their families, and patients with cancer.

UK Biobank, a large long-term biobank study in the United Kingdom, which is based close to Manchester in Stockport, is working on whole genome sequencing for all 500,000 of its participants.

These participants have also contributed a wide range of medical and lifestyle information that has helped to make this an incredible resource for studying all aspects of human health and disease.

The Human Genome Project also contributed to the development of new sequencing technologies that have made large-scale sequencing of a patient’s genome a viable diagnostics, all of which is contributing to the development of new treatment options for genetic disorders.

As well as helping us understand why some people are at greater risk of developing specific disorders than other, so we can work to reduce those risks.