Finding the Perfect Genes?

Despite a plethora of the “Men Are From Mars…” type of self-help books, many people still think that the differences between men and women are unfathomable. Others think of the differences in terms of broad stereotypes, i.e. women are more nurturing and men are more aggressive.

So it was with great interest that we read some new research that could drastically alter the way we think about what drives us to be who we are.  It turns out that male or female behaviors are regulated by very specific genes that can be turned on and off at will.

The research, which was conducted by scientists at the University of California, San Francisco, aimed to locate those genes that are influenced by the sex hormones- testosterone and estrogen– and that dictate male and female behaviors.

The research team, led by Dr. Nirao Shah, managed to locate 16 genes that were expressed differently in male and female mice and showed that the different expressions were regulated by the sex hormones. They found that they could isolate parts of classic male and female behaviors and pinpoint them as being governed by their own particular genes. They also noticed that each gene regulates a few components of a behavior without affecting other aspects of male and female behavior.

In other words, by flipping the switch, they could turn off a mouse’s sex drive, willingness to spend time with their young, and even their desire to pick fights while leaving every other behavioral element unaffected.

Imagine how crazy it would be if we could do that in humans.

Don’t like that your boyfriend gets into fights or that your girlfriend has “yet another headache?”  Simple…just flip the switch!

Fortunately, there are more serious applications of this research. Understanding the genes that drive male and female behavior could, for example, guide researchers to locate which genes are involved in diseases such as autism, which affects four times as many males as it does females.

As good as all that sounds, there is something a bit unnerving about contemplating your genes as a collection of switches that govern your behaviors. On some level it would be a dream to be able to turn behaviors off and on at will. While it would revolutionize the way we interact, it could also change our conception of what makes us who we are. Fortunately, manipulating them is a complicated process. So it looks like we’ll have to wait a while before we start popping pills to fine tune ourselves.

That’s a relief, because for most of us, managing the hormones we already have is a big enough job!

A new approach to new drug approvals?

Few topics inspire more heated discussion among drug developers and pharmaceutical industry watchers than the regulation of new products.  For those unfamiliar with the debate, the two sides of the argument can be summarized as follows.

Industry veterans feel that excessively conservative regulators squelch innovation in a desire to cover their own behinds, while industry critics contend that regulators aren’t strict enough, and that pharmaceutical companies should be held to an even higher standard and warrant even greater supervision.

In the meantime, patients wonder why modern science hasn’t produced the medicines they so desperately need.

Now it seems there may be an answer that could satisfy everyone.  Susan Desmond-Hellmann, Chancellor of the University of California, San Francisco (UCSF) and former Genentech executive, suggests turning drug approvals from a discrete yes or no variable into a continuous moving target.

The fundamental problem with the current system, Desmond-Hellmann observes, is that regulators have only two options, when in fact, it might make a lot more sense for them to have a range of choices. She proposes that agencies, such as the FDA, could approve a drug for limited use, or use with limited promotion, following the submission of initial acceptable evidence of safety and efficacy. Permission for broader use, and less restrictive promotion, could be given after additional data are obtained.

This solution appears to make sense on many levels. It acknowledges:

  • the long time it takes to become familiar with a drug and learn some of it’s more subtle effects – good, as well as bad
  • the importance of accelerating the time it takes to get potentially useful drugs into the hands of patients who might need them
  • the technologies now available to track and assess the performance of new drugs

FDA Approval Process

One advantage of such a system would be the emphasis it would place on durable results, as full approval would likely require not just success in a clinical trial, but continued demonstration of success under “real world” conditions.  Such a requirement would almost certainly stimulate the development of integrated “health solutions,” a bundled assortment of patient- and physician-support programs accompanying the drug.

Although a graduated regulatory approval process would not be perfect; it is almost certainly a significant step in the right direction.

Patient and physician educational and adherence programs make sense, but many companies have been reluctant to invest in them.  In the context of an offering that would need to succeed in order for a drug to be fully approved, the incentives are considerably more apparent, and would almost certainly stimulate interest in companies striving to deliver the most effective patient support programs.

However, the big questions still remain.  Are regulators ready for such change? Is the Industry ready to take on the responsibility and cost of ensuring appropriate use of their products and long-term pharmacovigilance? Would patients and consumer watchdog organizations accept a tiered approach?

What do you think?  SRxA’s Word on Health would love to know.