Dad can affect baby’s health

I saw this blog post referencing an article I wrote for the Raleigh News & Observer.

 I really just wanted to make 3 comments on it:

1) The blog post really goes where I never ever expected it to go, which is why I had to share it.

2) The author uses my first name. It appears only women are prone to this infantilizing treatment. Yay.

3) It would have been really cool to have made this one research paper part of a longer story explaining epigenetics. I think a good percentage of newspaper readers (sadly not 100…) get genetics, and epigenetics would blow many of their socks off. If they are above a certain age (not very old!) they certainly wouldn’t have learned it in high school and perhaps not even in college.


Naked Mole Rats FTW

I have seriously been told I resemble a naked mole rat when I’m roused from sweet, sweet slumber. My eyes refuse to open, and I burrow under the sheets. I’m pretty pale and mostly hairless, too.

While I hope I don’t resemble a naked mole rat in all ways (a bit on the uncomely side) I think there’s reason to hope my cells act like their’s.

Naked mole rats never get cancer.

It appears they don’t get cancer because their cells experience “contact inhibition.”

Humans get cancer quite a bit, and the odds increase as we age. The chances of a cell switching to cancerous increase, simply because we’ve given them more chances to do so. Lab mice get cancer about 70% of the time, if allowed to live for several years.

Human and mouse cells experience this contact inhibition phenomenon as well. Cells divide and fill up the space they’re in. Once they touch, they generally slow down their division; there are enough cells.

Cancer cells don’t have this contact inhibition, and grow wildly, unchecked.

Naked mole rat cells, when studied in the lab, exhibit a super kind of contact inhibition – cell division completely stops when cells touch.

In the future, perhaps we can identify what causes this, and turn on a switch in our own bodies if we suspect we have cancer.

Real nanobots !!!! (???)

With fancy chemicals being developed for new medicines, a question remains: how can we deliver the most bang for the buck? It would be ideal to have a microscale delivery truck, capable of delivering the drug to the precise location needed. This would also eliminate many side effects experienced through a general delivery of the drug.

 Catalytic nanoswimmers are being researched as potential cargo vehicles. They are tiny spheres, with one half coated with a reactive material. This side reacts with chemicals in the environment, and the energy of reaction is transmitted into motion forward. Attach a blob of drug to them, and they can move medicine. But questions remain about how to get them to go a specific direction, without having to babysit them. Can we make these trucks driverless?

One way to direct these particles is to establish a fuel concentration gradient. The particles will be ‘attracted’ to the hot spot, though they have no free will.

In a recent paper, researchers say while this approach is interesting, it can’t be the solution. After all, the fuel molecules are not necessarily always the signal you want the swimmers to react to.

They explore another signal: a pH gradient.

Hydrogel particles can swell or shrink in size when the acidity of the environment changes. Particles are  smaller in high acidity, and larger in low acidity. By exposing hydrogel catalytic swimmers to a pH gradient, the team was able to accumulate the swimmers in high pH regions. Cancer cells, as an example, can cause acidity changes.

So why does this accumulation happen? First, the high pH makes the particles larger, which makes their diffusion – the random motions experienced at the microscale – slower. Thus (smaller) particles in low pH regions will be kicked out more often, and settle in the high pH region. The smaller particles also undergo more (random) rotational motion, and this ends up being a double whammy for remaining happy in low pH regions.

I was struck by this paper as it was in nice contrast-and-compare to the run-and-tumble motion of E. Coli. bacteria, as is mentioned in the paper. Both systems are governed by the same physics, at the same scales. E. Coli turns its motor off to tumble and rotate, and figure out where the food is. It then turns the motor back on when it finds somewhere to go.  The catalytic swimmers have no such on/off switch, but can still get to where they need to go.

AWIS meeting report

Here is a report I did on the AWIS Philadelphia meeting. The topic was ethical considerations when pharmaceuticals and academic medicine mix. I am posting the full text here, or you can go to the AWIS-PHL website for a pdf version.


October 2010 Meeting Report by Kerstin Nordstrom

Kathryn Ross (MBE, DMH (c)), the Research Coordinator for Quality Research at the American Board of Internal Medicine, gave a presentation entitled “Pharma’s Ties with Academic Medicine:“Ethical Concerns?” on October 19th at The College of New Jersey. This was a joint meeting between the Central New Jersey and Philadelphia AWIS chapters. She opened by formally defining a conflict of interest, a key issue for any ethical concern. A conflict of interest is a set of circumstances that create a risk that actions regarding a primary influence (e.g. patient health, research validity) will be unduly influenced by a secondary influence (e.g. financial gain) [1].

Conflicts of interest (COIs) are present in every stage of life as a physician: in medical school, in residency, in practice. Ms. Ross presented results of a survey of residency programs conducted by the ABIM. Program directors and senior residents were asked, “What constitutes a conflict of interest?” There were several striking differences between the two groups. For example, 61.8% of senior residents classified excessive moonlighting as a COI, contrasted with 79.4% of program directors. Other notable differences were: personal use of sample medication (73.4% vs. 82.5%), accepting pharmaceutical gifts/meals/entertainment (75.8% vs. 89.7%), and accepting unrestricted educational grants (62.1% vs. 17.5%). The survey further went on to ask, “What is allowed at your institution?” The notable differences of opinion were: pharmaceutical detailing of residents (14.9% vs. 33%), distribution of free educational material such as textbooks (34% vs. 56.7%), industry support of continuing medical education (13% vs. 47.4%), unrestricted educational grants (6.8% vs. 80.4%), and faculty serving as paid consultants (26.3% vs. 61.9%). Clearly, the survey results indicate a discrepancy that points to a lack of clear COI guidelines. The survey further found about half of the programs had COI guidelines for trainees, about half had COI curriculum, but only a small percentage (<10%) had any COI competency evaluation for trainees.

Additionally, there was a difference in the opinion on unrestricted educational grants (UEGs) between university settings (22.4% classified UEGs as COIs) and community settings (12.7%). This may reflect that university settings are more likely to be pharm-free. One might come to the conclusion that academic settings are then doing “better” with regards to COI than non-academic settings. Perhaps, but the overall results of the survey also show that neither setting is doing especially well in establishing clear guidelines. Also, academic settings are in a better position to effect change from the ground up by actually instituting formal COI curriculum.

Ms. Ross went on to emphasize that the stigma attached to the term “conflict of interest” must be thrown out. Conflicts of interest technically only refer to situations where there is risk of undue influence. Classifying a situation as a conflict of interest does not mean any transgressions have occurred. In other words, COIs do not necessarily need to be abolished (though specific kinds may be); there is simply a need for clear COI policies.

In fact, many conflicts of interest have positive aspects that ensure they are around to stay. An example is the industry financing of medical research. All three parties potentially benefit: industry may develop a new product, academia may discover an effective treatment, and ultimately the patient is the beneficiary. These benefits must be weighed and discussed openly against the main risk of the COI: the patient’s health may be influenced by the profit motive of industry. However, as long as this COI is disclosed and discussed openly, action can be taken to minimize risk.

Therefore, in order to effectively deal with COIs, the first step is disclosure. However, evidence suggests even this basic first step is not always undertaken. In another study [2] a sample of 41 paid medical device company consultants was taken. From this number, 31 had published an article on their research. Of the 31 papers, 25 were randomly selected. None of the 25 articles published COI disclosure. This points to a need for a standard practice for disclosure. A standard practice would not only increase the rate of disclosure, it would also reduce the burden for disclosing. An indirect benefit is that this would create a larger data set on which to base policies.

Once disclosure practices are in place, the next step needed to address a COI is to assess the likelihood and severity of harm. As medical COIs usually involve patient health, this step is critical. Finally, one can determine if a COI needs to be prohibited outright or may be managed.

The timing of the meeting was serendipitously on point. Just two hours earlier, NPR and ProPublica began broadcasting the results of their “Dollars for Docs” investigation [3]. Under the recent Health Care and Education Reconciliation Act was included a law called “Physicians Payment Sunshine Provisions” where all pharmaceutical companies must disclose all financial transactions with physicians starting in 2012. Some companies have started doing this already, and the investigation tracked the payments. The investigators looked at 384 of the highest paid consultants and found that many had no board certification and many had allegations or convictions of professional misconduct. Additionally, several of the companies had recently settled massive lawsuits regarding the promotion of off-label drug use. While these examples may simply be “bad apples”, clearly this does nothing to placate public notions that industry may be “buying” or influencing doctors in unsavory ways. With better COI procedures in place, doctors and industry may hope to win back the trust of the patient.

Interestingly, the nature of industry influence is evolving as well. Historically pharmaceutical companies have been able to get prescription data from pharmacies. They can then target their marketing to specific doctors with data mining. However, some states have recently restricted this practice. Anyone with a television has seen the result of these measures: an exponential increase in direct-to-consumer marketing because of this restricted access to physicians. The patients’ involvement in the marketing only compounds the complexity of COIs, underscoring the need to address them.

While some previous examples paint an unflattering picture of some companies, it is important not to demonize the entire pharmaceutical industry. Many companies have their own sets of ethics guidelines and may follow them well. Companies are also in business, so it is unfair to judge them for desiring to increase sales or to develop a new drug. Further, they are the experts on the drugs/devices, and so are the informational authorities. Certainly many COIs in academic medicine could be avoided if all research funding was pharm-free and all medical education funding was pharm-free. But neither option is realistic in our society. Therefore, it is important to establish clear guidelines regarding COIs and to begin to establish formal COI training.

Ms. Ross ended the presentation by summarizing a recent meeting report from the Institute of Medicine [1]. The report summarizes recommendations to help medicine address COIs. Recommendations for academic medical centers (AMCs) are organized into three main points: 1) At AMCs, Prohibit gifts, ghostwriting, speakers bureaus, and limit drug samples, consulting, sales representatives. 2) Provide education on relationships with industry and COIs. 3) Develop a new system of funding accredited continuing medical education that is free of industry. Hopefully, AMCs can adopt these policies and standardized practices will result in the future.

While some might dismiss professional ethics as a personal rather than professional skill, the bottom line is over 90% of physicians get some form of industry support, and practically all medical research is industry-funded. While this is not necessarily a bad thing, many of these relationships necessarily entail conflicts of interest. It is of utmost importance to ensure these COIs are well-managed and prohibited when necessary. By managing them effectively, patients may be assured that their doctors have their best interest in mind: their health.

The presentation was followed by a fruitful discussion with the audience as well as a tour of our host institution’s science facilities.

[1] Conflict of Interest in Medical Research, Education and Practice, IOM, April 21, 2009
[2] Chimonas, Susan, Frosch, Zachary, Rothman, David J. “From Disclosure to Transparency: The Use of Company Payment Data” J Arch Intern Med (2010)