As all the world knows, two teams of researchers, the private company Celera Genomics and the International Human Genome Project, have succeeded in sequencing all human genes. The results of these landmark investigations are being published in Science and Nature this week. One of the important things we've learned from the experience is that competition matters. Without pressure from Celera, the public project would likely have continued its stately progress toward completing the human genome by 2005.
What else have we learned? First, that it takes around 30,000 genes to make a human being. By contrast, it takes 13,600 genes to make a fruitfly and 19,000 genes to make a nematode worm, whose entire body contains only about 1,000 cells. The fact that it takes only a few more genes to distinguish a worm from a man has prompted some observers to wax poetic about the "unity of life" and to suggest that it will be "a source of humility and a blow to the idea of human uniqueness." This is silly. While genes clearly constitute the recipe for making human beings, our uniqueness resides in our brains and the culture that arises from them. Our genes have met their match. In the future they will no longer control us (to whatever extent they do now); we will control them. Human dignity resides in our brains, not our DNA.
Second, that the genes which actually make the proteins that comprise our bodies are only 1.1% to 1.4% of the 3.2 billion base pairs that make up the entire human genome. Most of our DNA appears to consist of genetic parasites.
Third, that what was once called the "central dogma" of biology--one gene makes one protein--has been overthrown. The central dogma still apparently applies to many simpler organisms, but some human genes can, through alternative splicing of their DNA, code for as many as 10 different proteins. This is what accounts for the complexity of the human body and brain, which is composed of as many as 250,000 different proteins.
Fourth, that there is relatively little genetic variation among people. As a very young species, our genes are 99.9% the same as each other's. Evidence from the human genome strongly points to our species arising from a population of as few as 10,000 individuals in Africa within the last 150,000 years or so.
Fifth, that researchers can now probe the variations between human beings. Most of those differences are expressed in what are called single nucleotide polymorphisms (SNPs--pronounced "snips"). SNPs occur when one DNA base pair is substituted for different one in equivalent stretches of DNA. It is estimated that between 1.6 million and 3.2 million SNPs will be found in the human genome. Researchers have identified 1.42 million SNPs so far, of which 60,000 occur within genes. It is those 60,000 SNPs that account for the differences between people.
Sixth, that genetic determinism is out the window. A lot of laypeople seem to buy into a notion that reads something like "one gene, one behavior." Genes do provide the recipe, but just like making a cake, one must add proper ingredients in the proper order and then bake them in a properly heated oven for a cake to appear. The recipe doesn't make the cake; the environment of the whole kitchen does. Similarly our genes are constantly adapting and responding to our environment--certain genes only turn on to produce proteins when certain influences or stresses are present. For example, genes that lead to heart disease by boosting lipid levels may only be expressed in the presence of a high-fat diet.
Seven, that the functions of the about a third of human genes are still unknown.
So what's next?
In a word, proteomics. A lot of companies, including Celera Genomics and Large Scale Proteomics, are investing in facilities to unravel the human proteome--the complete set of proteins encoded by the genome. As noted above, the number of proteins is many times greater than the number of genes. Determining how all these proteins interact is an enormous task compared to sequencing the genome, which is essentially a straight digital readout of DNA pairs in a defined order. In the body, proteins combine in thousands of complicated networks that are only now being described.
Considerable light will be shed on the human genome as other genomes are sequenced. So far, the genomes of more than 60 species, including a lot of bacteria, the nematode worm, the fruitfly, yeast, rice, and mustard weed, have been fully sequenced. That will rise to 100 in the next few months. Already, researchers have discovered that some 60% of human proteins are similar to proteins found in other species. Celera has already done a first draft of the mouse genome. Company chief Craig Venter says that he has found only 300 human genes that have no counterparts in the mouse. (Thus, genetic and proteomic research using mice will be very useful for illuminating normal--and disease--processes in human beings.)
Scientists have already found at least one disease-related mutation (or SNP) for 1,100 different human genes. Technologies like biochips will allow researchers to find out which suites of SNPs are associated with which illnesses. For example, one day researchers might find that there are 40 SNPs that together tend to increase one's chances of getting heart disease. A biochip could be designed so that a physician could check to see how many of these deleterious SNPs a patient has and on that basis advise the patient on lifestyle changes and recommend medications tuned to his or her specific pattern of SNPs to protect his or her heart.
"With only 3000 candidate genes to work from, i.e., 30 for each of the top 100 companies throughout the world," one researcher wrote in Science, "the pharmaceutical industry is now facing a new challenge…developing leads for all these candidates should only take a few years of fierce competition." Thus, he concludes, "one can seriously question the long-term sustainable growth and economic viability of the whole industry."
It truly is a new era when people can seriously worry about what drug companies will do after they've cured cancer.