Gene therapy is still a bust for most diseases

The big science human genome project, which began in the 1990s, promised to offer personalized medicine. They said decoding the human gene would translate into new, personalized gene therapies. And who doesn’t like the idea of personalized medicine, tailored to your individual wants and needs? Yes, everybody is different. And not all treatments work well for everyone. That is an axiom of medicine.

But now–a generation later–I wonder where are all these promised, new gene therapies?

The gene therapies we do have don’t work. Plus, they can cause serious side effects.

In fact, earlier this year, American neurologists said they have no use for high-tech gene therapies. They voted against using genetic approaches to treat neurological conditions at the annual meeting of the American Academy of Neurology. They also said the new gene therapies are expensive, useless, and even dangerous to their patients.

The big science human genome project also promised that genetic research would radically transform disease prevention. And this promise might have come true when it comes to lung cancer, if the National Cancer Institute hadn’t stepped in 30 years ago.

You see, we have known for decades that differences in genes influence the effect (or lack of effect) of smoke on lung tissue. In other words, some people seem more genetically susceptible to smoke damage than others. And this observation makes sense when you look at the numbers. Just one in 10 people who smoke cigarettes ever develop lung cancer. So clearly, smoking isn’t the sole issue. Something else is at play–probably genetics.

Unfortunately, 30 years ago, newly minted behavioral science bureaucrats at the National Cancer Institute put a stop to that genetic research in favor of spending their entire budgets on controlling human behavior. Even for the 90 percent of smokers who didn’t need it, not to mention the other two-thirds of the population who don’t smoke.

I’m not the only one questioning this unproductive obsession with gene therapy.

Last month, in the Journal of the American Medical Association, Drs. Michael Joyner and Nigel Paneth from the Mayo Clinic and Michigan State University posed several cogent questions about gene therapy.

First, they said the human genome project doesn’t contribute all that much to predicting disease risk.

For example, even if you get an expensive genetic test and learn you do carry a certain disease gene (with all the worry that comes with it), that gene doesn’t actually impact your relative risk of getting that disease all that much. Let me explain…

The big genome project promised to identify genetic susceptibilities that raise a person’s risk of getting various diseases by six times over. But that simply never happened.

Instead, we now know the actual increased relative risks of these supposed disease-causing genes are rarely more than 1.5. In other words, if you carry said gene, you have a 50 percent increased risk on average of developing that disease.

Now let’s put that number into perspective…

We already knew that diet, lifestyle, nutritional, and reproductive factors have relative risks for common chronic diseases of 2.0 up to 4.0–meaning double, triple, or quadruple the risk. Why not concentrate on these larger risk factors that you can do something about–rather than focus on the lower risk genetic factors we can’t do anything about anyway?

Furthermore, research shows giving patients information about their genetic risk doesn’t change their adherence with the known lifestyle interventions that really do prevent diseases. So, “targeting” prevention to those at genetic risk has not yielded benefits either.

Of course, there are a few other downsides to genetic testing.

First, many people consider it an invasion of privacy. Second, having the knowledge that you carry a certain disease gene can adversely affect your job, your marriage, and your peace of mind. It can be stressful to know you carry a gene for a disease that nobody can do much about.

Genetic testing has gained some traction in the cancer world. For example, many oncologists now test for the BRCA gene for breast and ovarian cancers.

But is that information really all that helpful, as the JAMA authors asked?

By definition, cancer cells have different, abnormal genes than do normal cells. So theoretically, you should be able to develop a drug that would target cancer cells with these abnormal genes and leave normal cells alone, right?

Well, not so fast. The benefit of such drugs measured by overall cancer survival has been highly limited. And here’s one reason why…

Cancer cells adapt. And there’s little evidence that gene-targeted chemotherapy interrupts the cancer cell cycle. Instead, we have an endless cycle of expectation and disappointment that typifies every new mainstream approach to cancer therapy.

The much-publicized BRCA genetic test for breast and ovarian cancer has been useful for a small subgroup of the population. So–women who carry the BRCA gene now know they run a very high risk of developing breast or ovarian cancer. But no new therapies have resulted for these patients. Plus, genetic testing hasn’t contributed to reduction in mortality rates from these cancers, which is the ultimate goal for any treatment. With no real options, many women with the BRCA gene now opt for the drastic measure of complete mastectomy and removal of the reproductive organs–which takes us back to what cancer surgeons did a century ago before we had all this new genetic technology.

Truthfully, any real advances in cancer control have come from old-fashioned public health measures.

Genetic testing was also supposed to help doctors better match different drugs to different patients for other common diseases. But so far, that approach hasn’t worked out for the drugs tested, such as Tamoxifen and warfarin, which can have terrible side effects for some patients who turn out not to tolerate them.

Dr. Michael Holick, my colleague from Boston University’s School of Medicine, is leading the charge in one promising area of genetic research. Of course, his research relates to vitamin D’s influence on your genes.

In fact, Dr. Holick and his colleagues found that a vitamin D deficiency affected the expression of 66 different genes. And taking a modest vitamin D supplement (400 IU to 2000 IU per day) influenced the expression of 291 different genes. These included genes that helped with DNA repair. And immune response. And response to stress.

So while the high-tech medical research world continues to plough ahead down an expensive, dangerous, dead-end street, you can do something simple right now to support your healthy gene functions: Get more vitamin D.

At this time of year, try to spend 15 minutes a day in the sun without sunscreen to activate vitamin D production in your skin. Also–I now recommend everyone take 10,000 IU of vitamin D each day as a supplement year-round.


“Seven Questions for Personalized Medicine,” JAMA published online June 22, 2015.