Genes Do Not Cause Disease

Great time, effort, and money was spent in unraveling the human genome. A principal justification for that enormous project was the belief that identifying genes would unleash unimaginable health benefits: we (or at least gene technologists) would be able to manipulate defective genes or at the very least find out which gene variations are associated with the risk of disease and disability.

The Human Genome Project produced two big surprises. First, humans have far fewer genes than other organisms that are supposedly more primitive. The second surprise was that only about 3% of human DNA seemed to be doing anything. No one knew what the other 97% was doing. It was called Junk DNA.

Fairly quickly, scientists discovered that genes are actually networks of DNA. In other words, the work of understanding our genes moved even further away from the 19th Century idea of a gene as a single chemical that determined a single physical trait—for example, a gene for eye color, another for intelligence, yet another for disease risk.

Sixty years ago DNA was identified as the gene chemical. It maps the proteins that go about the life processes of cells, tissues, and organisms. As a result, the science of “the gene” was detached from traits and reattached to chemical reactions. The Human Genome Project moved this detachment even further along by prompting discoveries of the myriad ways in which collections of DNA segments are orchestrated to produce not just one but often myriad proteins.

Yet the old notion of one-gene-one-trait has clung to the science. It is the horse on which the science rides, carrying it through public and political fields to the citadels of research funding.

There’s no better example than recent research that promises to reveal what Junk DNA is doing. Published in Nature Structural and Molecular Biology, researchers at UC San Diego argue that although Junk DNA doesn’t produce proteins, it does produce RNA—an intermediate messenger that helps orchestrate the protein creation process.

The authors tell us that their work provides insight into the working of two genes associated with neurodevelopmental disorders, such as autism and certain cancers.

So we not only have a complex network of DNA for producing one or even many proteins, we have an even more extensive system of DNA that orchestrates or otherwise serves that process—and so we are even further from one gene, one trait. And yet daily reports attest to the attention and resources devoted to genetics based on this mistaken view. Not only daily reports, but enthusiastic campaigns to create things such as personalized medicine based on individualized genome analysis.

I think there are two fatal flaws to following this path.

The first fatal flaw is that the new Junk DNA science and some other recent results provide good reason to believe that current so-called advances in medical technology based on older models of how genes and cells work is wrong—or at least wrong enough that the technologies cannot provide reliable results. People subjected to them would simply be experimental subjects: might work, might not.

The second fatal flaw is that there’s no reason to believe any technologies based on the new understanding of gene expression will be any more successful than current technologies based on the old understanding. Although many are still enthusiastic, after a decade of work flowing from the Human Genome Project there’s very little in the gene-based medical repertoire that works—no cure for cancer, heart disease, or much of anything else.

What all of this does demonstrate is the deep and abiding commitment of conventional medicine and public and private funders to the 19th Century idea that, by identifying the piece of your biology responsible for illness, some clever boy or girl engineer can fix it. The problem is you. And we (the engineers) can fix you.

On the other hand, the Robert Wood Johnson Foundation launched a program several years ago that sprouted a catch phrase: zip code is more important for health than genetic code. The Program’s most recent report “Overcoming Obstacles to Health in 2013 and Beyond” concludes, among other things, that

• For both men and women, more education means longer life;

• Compared with children in the high-income families, children in poor families are more than four times as likely to be in less than “very good” health; and

• Health differs not only by race or ethnicity but differs by income within each racial or ethnic group.

This is a far more powerful way of approaching health and illness than genetic identity and manipulation. It’s more powerful because of something quite obvious, something even genetic technology enthusiasts know: our genes, our DNA-based biological chemistry not only responds to our environment, it is the environment that ultimately orchestrates our biological chemistry. And we are the ones who cause that environment to wither or flourish—and ourselves along with it.

Earlier I mentioned two fatal flaws to the commercial and scientific love affair with gene research. There’s a third: gene science as the focus of health science consists of answering the wrong question. The British epidemiologist Geoffrey Rose observed that when environmental causes of illness are removed, susceptibility (genetic or otherwise) doesn’t matter because there’s nothing there to provoke our biological chemistry.