By Dov Michaeli

If you haven’t heard about the science of genomics you must be living under a rock. Genomics surveys thousands of genes at a time and tries to find patterns, or signatures, that correlate with specific diseases. The hope is that you could then design drugs specifically tailored for these genes, and voilá-a cure was born. Sounds straightforward, except it isn’t. Patterns are just correlates, not necessarily causal. Furthermore, the genomic signature obtained from cancer cells of one patient may be radically different from another patient with the same cancer. And to make things even more complicated, analyzing those patterns from many patients requires digesting a huge amount of data with what is called data mining, employing highly complex computer algorithms. And making sense of those data requires extremely complex statistical analyses. All this suggests a great potential for error –and this indeed plagues the field right now.

Now, even if you haven’t lived under a rock and diligently tried to keep up with medical development I’d bet you haven’t heard about the branch of research called metabolomics. So let me explain.

The classical way of studying the putative cause of a disease, say heart disease, is to start with a suspected molecule, say cholesterol, and measure its effects, like LDL levels in the blood or atherosclerotic plaque formation in blood vessels. You can easily spot the weakness of this approach –it is akin to describing the content of a room by watching from the outside through a tiny peephole; you can describe only what you see, which is by necessity extremely limited.

 Enter metabolomics. In this approach researchers try to identify thousands of small- molecule metabolites in a system and determine the relationship of the totality of these molecules (called metabolome, a lá genome for genes) to disease.

Diet, gut, blood and heart

In a paper published in the April 7, 2011 issue of Nature Wang and his coworkers provide a great example of the power of metabolomics: they uncovered a fascinating chain of events that is linked to heart disease.

The researchers searched for circulating small molecules associated with coronary heart disease. They screened blood from patients who had a history of a heart attack or stroke and compared the results with those from blood of people who had not. What they found was surprising. A dietary molecule called lecithin, found in high fat foods like meats and egg yolk, gives rise to a metabolite called choline, which is an essential nutrient, and deficiency of which can cause non-alcoholic liver disease and muscle damage. How lecithin converts to choline turns out to be unexpected: not by our intestinal enzymes, but by bacteria residing in the gut. But that’s not the end of it: choline is then converted to TMAO (trimethylamine N-oxide) in the liver. And this molecule turned out to cause the formation of atherosclerotic plaques in mice prone to atherosclerosis. To further nail the chain reaction of dietary lecithin –gut flora –choline –TMAO –atherosclerosis they showed that elimination of gut bacteria with broad-spectrum antibiotics eliminated TMAO formation and plaque formation ( don’t try that at home –it was done only for experimental purposes). Furthermore, when they infused TMAO to the antibiotic-treated mice atherosclerotic plaques were formed.

So here we see the power of metabolomics: by looking at a disease through a large window rather than a small peephole, a molecule that was not suspected of doing any harm was discovered.

What should we do about it in “real life”? Should we eliminate lecithin from the diet? Of course not. Lecithin, and it metabolite choline are essential nutrients, as we said. But if you go into any health food store you’ll find lecithin and choline pills, with claims of reduction of the risk of heart disease and improvement in muscle strength. Body builders pop these pills like candy.

 And that’s where the problem lies: we tend to think if something is good, more is better. And as always, there is a political aspect to it.

You would think that the FDA would ban health claims where there is no evidence to substantiate them. Think again. Courtesy of your friendly senator from Utah, Orrin Hatch, the FDA is specifically banned from demanding such evidence from the nutritional supplements industry. Why should the good senator Hatch take such an interest in protecting this dubious industry? Because much of the industry is located in Utah, and is donating princely sums of money for to campaign. Oh, yes; his son happens to be a lobbyist for the nutritional supplements industry association.

So don’t wait for the FDA to alert you to the risks inherent in nutritional supplements –just say no. Eat well, and if you insist –take a multivitamin pill. But stay away from those dodgy suppplements.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

1 COMMENT

  1. Thank you for the intelligent summary on genomics. As a one year ovarian cancer survivor, I understand the passionate belief that modern science, fueled by dramatic developments in DNA and genomic research, has finally delivered the “cure”. But as you point out, there is still a long road between scientific data and clinical treatments, with many pitfalls along the way. Thankfully, we are opening new doors every day. But after many months of diligent hopeful searching on my own behalf, I continue to embrace the proven science. As to the news door, I must know much more about what is behind them before I enter.

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