Is Bill Nye really helping science?

billnyesaves-630x240

So, Netflix Canada has started showing Bill Nye Saves the World, a science series designed for adult audiences, and in the first two episodes, he has tackled issues such as climate change and alternative remedies. The premise of the show is that Nye will use the scientific method to debunk the myths.

In theory, I am all for this approach. Unfortunately, the entire show is theory. In two episodes, I have seen nothing of a scientific method.

Episode 1: We’re going to heat a liquid to show you that heat causes things to expand. We’re going to tell you that CO2 is a greenhouse gas and that things get hot because the gas traps heat energy. The rest of the episode is mostly just people yelling about how silly deniers are.

Nye greenhouse

Bill Nye, the gimmick guy

Episode 2: Magnetic patches don’t cure disease because there is nothing to magnetically attract in the body. Oh, and this is how clinical trials work. But we’re not going to test magnetic patches in a clinical trial because we don’t have to. There was one scientific experiment to show that Milk of Magnesia neutralizes acid while a Whole Foods purchased stomach remedy did nothing to neutralize acid. Thing is, there is more to upset stomach than acid neutralization, and we don’t know the mechanism of action of a lot of FDA-approved medications. The rest of the episode was Nye yelling “that’s stupid” (not literally).

Despite his self-proclaimed mission, Nye seems to be playing into the hands of the anti-science faction by trying to cram complicated subjects into 30-minute windows of reality-style television that is more Jerry Springer than Mr. Science.

Nye-Springer

Ridiculing the other side with unsupported taunts and name-calling is NOT good science. Shoddy, make-shift experiments that don’t actually prove your point are NOT good science.

If you say claims have not been supported by scientific evidence or clinical trial, then run those studies to prove the claims aren’t true. THAT is good science. But it is lousy television.

So, Bill Nye; are you a television personality or a science advocate?

If you remain the latter, then cut the bullshit and get back to the method.

If you are the former, then take off the lab coat, and I’ll go back to Thomas Dolby.

 

Malnourished with malinformation

KnowledgeI’d argue that any amount of knowledge is a good thing. It is a little bit of information that is likely to trip you up.

As many of you know, I am a science and medicine writer in another life—the more lucrative one, but that’s not saying much—and so I spend many of my days immersed in the worlds of scientific and medical discoveries and blundering. I even spent several years working at a biochemistry bench as a scientist—you may genuflect, now—so I know the world of which I speak.

For this reason, I tend to view science and medicine as a work-in-progress, as so much noise with moments of signal. Rarely do I herald the hype and equally rarely do I despair the bumps.

To my friends who see every announcement as a breakthrough, I am a cynic. And likewise, to everyone who pounces on every setback as evidence of mass conspiracy, I am a complicit shill. Whatever.

The challenge comes when I engage in a discussion of the topic du jour, because more often than not, the person with whom I am talking is adamant that he or she knows the truth. They are empowered by something they have heard or read from a renown expert. They have information.

(Let me state here that I do not believe that I am the holder of all truths. I do feel, however, that I have a good handle on what I do not know, and just as importantly, what is not yet known for certain.)

So, let’s start with some definitions (purely mine) of information types:

Information: A collection of facts about a subject upon which someone can formulate a testable theory or postulate a conjecture.

Misinformation: Incorrect declarations that potentially lead one to false conclusions.

Disinformation: Knowingly false declarations for the purposes of misleading another group (e.g., counter-espionage, propaganda).

information triangle

I suggest, however, that we need another category to address the shade of grey between the positives of information and the negatives of mis- and disinformation.

Following the model of nutrition versus starvation, I propose we call this new category malinformation, with the following definition:

Malinformation: A collection of facts that, while true, is insufficient to formulate a definitive conclusion without the support of further facts.

Just as a malnourished person is not starving, but rather suffers the effects of an insufficient blend and quantity of nutrients to experience balanced health, a malinformed individual is not wrong per se, but rather suffers the effects of an insufficient blend and quantity of facts to experience balanced knowledge and understanding.

For example, people who change their eating habits because they read about a single study that showed a specific food extract reduced tumour size in mice. Or a clinician who has created a behavioural modification program to reduce addiction based on a thought exercise using largely unrelated studies.

Any of these decisions are based on legitimate data from legitimate studies, but often ignore (or simply don’t look for) alternative and/or possibly conflicting data from equally legitimate studies. Rather than analyze all available data before generating a theory, they find the malinformation that supports their beliefs and then stop; a little bit of data being taken to conclusions that simply are not supported.

Boom-bust

Maybe they’re right. But more likely, it is much more complicated.

In conversation, I find the malinformed much more intractable than the ill-informed. With the latter, there is a chance you can correct the misinformation. With the former, however, the mere fact that the malinformation is correct seems to be sufficient cause for them to defend the castle they have built in the sky. When you “yes, but” them, all they tend to hear is the “yes”.

In fairness, all information is technically malinformation as we will never have access to the complete knowledge of the universe. We are always going to be forced to make decisions based on limited knowledge.

But where more knowledge is available, I think there is duty to examine and understand it before becoming intractable in our positions.

If there is a newspaper article about a new scientific discovery, efforts should be made to learn more about the limitations of the science that led to the discovery. How far can you realistically extrapolate from those few data points?

In biomedical research, that which occurs in a mouse is, at best, a clue to what might happen in a human. Nothing more.

It could lead to the next step in scientific inquiry—the actual purpose of science—or to a dead end.

Belief is nice, but unless that belief is well founded on broad and balanced information, it is limiting and might be dangerous.

(Or at least, as far as I know based on my understanding of the available information.)

Substance over volume

ddnews

When you meet someone who does not speak your language, there is a cliché response of talking louder to make yourself understood. There is something within many of us that says if we simply pump up the volume, we can overcome the disconnect.

A couple of months ago, Tufts University released their latest estimates for the average cost of developing a new drug: $2.6 billion (I’ve seen estimates up to $5 billion). Eleven years ago, the same group calculated the costs at $0.8 billion.

Now, every time these estimates arise, the hand-wringing begins over how the costs were calculated, which factors make sense and which are over-reaching. What no one seems to argue, however, is that drugs are less expensive to develop today than they were a decade ago.

So what has this to do with speaking louder?

The same period has seen amazing technological achievements designed to facilitate and accelerate drug discovery and development.

Combinatorial chemistry was heralded as a way to expand compound libraries from hundreds to hundreds of thousands. High-throughput and high-content screening, as well as miniaturization and automation, were lauded as ways to screen all of these compounds faster under the paradigm of “fail early, fail often”. And given the masses of data these technologies would churn out, the informatics revolution was supposed to convert data into knowledge and knowledge into healthcare.

And yet, for all of these improvements in throughput, I question whether we have seen much improvement in the number or quality of drugs being produced. We certainly haven’t made them less expensive.

Please understand, I don’t place any fault in the technologies. These are truly marvels of engineering. Rather, I question the applications and expectations of the technologies.

Almost two years ago, GSK CEO Andrew Witty told a London healthcare conference: “It’s entirely achievable that we can improve the efficiency of the industry and pass that forward in terms of reduced prices.”

The pivotal question here, I believe, is how one defines efficiency.

I wonder how many people simply felt economies-of-scale would improve discovery, much as mass production made Henry Ford a rich man. But drugs are not cars, and where throughput and scale make sense when you have a fully characterized end product, they have their limitations during exploration.

When I was a protein biochemist in an NMR structural biology lab, I spent some time trying to wrap my head around two concepts: precision and accuracy. A 3-Å protein structure is very precise but if the structure isn’t truly reflective of what happens in nature, it is meaningless. A 30-Å protein structure is much less precise, but if it is more accurate, more in tune with nature, then it is likely more useful.

By comparison, I wonder if our zeal to equate efficiency with throughput hasn’t improved our precision at the cost of our accuracy. If you ask the wrong question, all of the throughput in the world won’t get you closer to the right answer.

In researching the DDNews Special Reports over the last couple of years, I have spoken at length to several pharma and biotech specialists about this topic, and many feel that the industrialization of drug discovery and development has underwhelmed if not outright failed. Several have suggested it is time to step back and learn to ask better questions of our technologies.

But getting back to the costs issue.

I know many will rightly point out that the largest expense comes from clinical trials. To address this challenge, new technologies and methodologies are being developed to get the most useful information out of the smallest patient populations.

Here again, however, no one segment of the drug development process stands in isolation, and I think back to the compounds reaching the clinic and question the expense of incremental improvements.

Oncolytics CEO Brad Thompson discussed the challenge in Cancer in the Clinic (June 2014 DDNews).

“If you could double [overall survival], you could show that in a couple of hundred patients. If you want to do a 10-percent improvement, you’re talking thousands of patients to do it to the statistical level that everybody would prefer to see. How do you run a study like that?”

That is a huge difference in financial expenditure that begs the question is an efficacy improvement of just 10 percent of value.

From an individual patient perspective, assuredly. From a pharmacoeconomic perspective, maybe not, and particularly with the growing prevalence of high-cost targeted biologics. Maybe we need to aim for bigger improvements before moving candidates forward, which happens long before the clinic.

Again, I’m not placing blame. The history of any industry is filled with experimentation in different methodologies and technologies. Everyone involved had the best of intentions.

But after a couple of decades of middling results, perhaps it is time to question how and when many of these advancements are applied. Simply yelling at a higher volume doesn’t seem to be enough.

[This piece was originally published in the January 2015 issue of DDNews. A lot has happened in the year since, including some amazing results in the field of immuno-oncology that might just address the demand for high-performance treatments even if only for a select patient population. For more on that, see my June 2015 Special Report “Body, heal thyself”.]

When numbers fail (DDNews commentary)

Dutee Chand

Athletics bodies have questioned whether sprinter Dutee Chand has an unfair advantage.

What is normal?

The question may sound absurdly philosophical, particularly for the pages of DDNews, and yet healthcare directly or indirectly deals with this question on a daily basis. And the clinical response can be as life-altering as the societal and political responses that we see on the news every night.

An entire industry has been created to test and monitor health using various diagnostic assays, to the most recent of which DDNews dedicates an entire section. In some cases, the results of these assays are binary—the classic example is being a little bit pregnant. But in most cases, healthy (or normal) falls within a range of values—think LDL/HDL, blood glucose or body temperature.

In part, this is a recognition that results can vary within an individual throughout the day, and on the larger scale, because individuals are products of their genetics and environments. What might be a healthy level for me in Toronto may actually be limiting in Johannesburg.

But even with the recognition of variability, we must always be vigilant in questioning how the normal range was defined. Was it based on the combined results of 200 male Manitoba bush pilots (I have read such a study), or a sampling of tens of thousands of individuals from around the world? If only for economic reasons, the former is more likely to be the case.

In 2011, Boston University’s Shalinder Bhasin and colleagues examined this challenge by identifying reference ranges for testosterone in healthy men. Suggesting that these ranges “have been derived previously mostly from small convenience samples or from hospital or clinic-based patients,” they examined a much larger cohort from the Framingham Heart Study (Gen 3), publishing their results in the Journal of Clinical Endocrinology & Metabolism.

Although most values were consistent with historic values, their lower limit of total testosterone was higher than that used historically but was “closer to the thresholds associated with sexual and physical symptoms in a recent investigation of older men.” Thus, when it comes to testosterone, it seems (sample) size matters.

But what about the outliers, the norms who don’t fit the norms and the unwell who do?

As a bit of a sidestep, just over a year ago, the International Association of Athletics Federations (IAAF) banned Indian sprinter Dutee Chand from competing in sanctioned competitions because her blood testosterone levels fell into the normal range of male athletes rather than that of her female competitors. Thus, the group decided, she would have an unfair advantage over her fellow runners.

What made this ruling particularly challenging, however, was that Chand’s testosterone levels were natural; they did not come about from doping. Her levels simply fell outside of the clinically accepted norm for women.

Closer to home for me are two friends who live with symptoms of hypothyroidism and have resorted to alternative medicine because they were dissatisfied with the medical establishment. In both cases, standard thyroid function tests suggest they fall within the normal range and therefore would not benefit from standard treatment. This may be true, but neither knows because it was never tried.

Admittedly, these are anecdotes. Three women struggle because they do not fit ascribed definitions, whether of health or pathology. And for every anecdote I can list, the healthcare establishment can rightly point to hundreds if not thousands of individuals who fit the defined ranges of normalcy.

It’s a conundrum I have discussed previously: healthcare is population-based while health is personal.

In our zeal to standardize healthcare and make medicine more scientific, we have to be careful not to ignore the natural variabilities of individuals within those populations. So-called normal ranges should suggest action, not dictate it.

Even as we pursue the precision medicine mandate, spending billions (and possibly trillions) of dollars on expanding our understanding of human biology and generating technologies to value every facet of it, we have to make sure that our knowledge doesn’t blind us to the patient’s truth. If that happens, if all we accomplish is a bigger monolith, then we have failed in the mission.

As to Chand’s racing career, the Court of Arbitration for Sport recently overturned the IAAF’s rule, giving them two years to prove that the higher testosterone levels truly give the runner an unfair advantage.

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Originally published in DDNews in September 2015, this is one of a series of commentaries I write each year. If you’re interested in recent technological and business innovations in biotech, pharma and healthcare, you should check the publication out.

Off the pedestal, Western medicine

hubris

Western medicine can be a smug son-of-a-bitch. Seriously.

Now, it would be unfair to lump this attitude on all practitioners of Western medicine, but I haven’t the time to survey all of its adherents and gauge individual opinions so that I can name names of those who are the smug bastards and those who believe in thoughtful open-minded consideration.

To provide some context, I have a B.Sc. in molecular biology and a M.Sc. in medical genetics, and have written about the latest biotechnical and biomedical advances for about 15 years. I have also written about Western medicine for about 7 years.

Given this background, it may seem odd to some that I am writing a complaint about the attitudes of Western medicine, but what may not be as obvious about that background is the amount of hubris and self-satisfaction I have seen in questionable practices with limited benefits.

Old wisdom isn't useless because it is old

Old wisdom isn’t useless because it is old

Recently, there was an article in New Scientist magazine that described the rediscovery of a possible treatment against superbugs (e.g., MRSA), a therapy chronicled in an Anglo-Saxon era manuscript. The roughly 1000-year-old remedy is being studied in a modern lab and early results suggest that it may prove effective against the bugs that threaten modern lives on a weekly basis.

(BTW, there is a thousand miles between early results and coming to a pharmacy near you.)

But what struck me most was the response to the findings in various media, which bordered on shock and awe that something relevant to today could come from such an ancient source. Even CBC’s The National (Canada’s national news broadcast) commented that the discovery came from an era when leaches were considered good medicine.

Which leads me to scream:

Science wasn’t invented in 20th century, people.

The grand assumption seems to be that anything that happened in medicine before the First World War was complete voodoo and not worthy of consideration in an era of rational thought.

Everyone involved in health remedies before the modern medical era was either a charlatan or a moron, and either way was dangerous to the people around them. The human capacity for sober scientific enquiry did not occur until shortly after the invention of the Erlenmeyer flask, the spectrometer and the harnessing of the X-ray.

I call bullshit.

If you can grind it or infuse it, you can medicate with it

If you can grind it or infuse it, you can medicate with it

Folkloric medicines are based on scientific inquiry by people without test tubes and spectrometers. The approach may have been less statistical in nature, but everyone from apothecaries to shamans (shamen?) ran clinical trials the old-fashioned way.

Take this. Do you feel better? Great. It’s a keeper. Did you die? Yes. Nuts, try something else on the next guy.

Having actually looked at modern clinical trials, the only differences between then and now are the test patient population size and the accounting of the results. And I don’t know that we can say definitively that these parameters have improved things.

I am not advocating that we discard modern medicine—it has merit—but rather than it must get off its high-horse and approach historical medicine with an open mind so that more rediscoveries like this latest one can happen and be tested.

TCM has worked for millennia

TCM has worked for millennia

China has about 20% of the planet’s population, so there might be something to Traditional Chinese Medicines (TCMs). The same goes for India and folkloric Indian medicines (FIMs). Or Anglo-Saxons or Sumerians or the indigenous peoples of the Americas. These people were not morons.

Our ignorance and outright hubris is a hangover of the Age of Reason as we dismiss everything that came before because it was often presented in raiments of spirits and ritual.

Modern does not guarantee success

Modern does not guarantee success

We should not let our fascination with the instrumentational bells and whistles of the modern scientific method blind us to the wonders of the not-so-modern scientific method, which lacked in instrumentation but not in knowledge and understanding.

Before you blithely dismiss something as troglodyte quackery, perhaps you should ask yourself:

What would Hippocrates do?

And as to the CBC’s comment about the era of leeches, both leeches and maggots have a long history up to this day of facilitating health in people (see Leeches and Maggots).

Showing concern

One of the myriad gulls sharing the local boardwalk

One of the myriad gulls sharing the local boardwalk

There are truly good people yet in the world.

As some of you know, I am going through a bit of a problem with one of my shoulders (a condition with the stupid name frozen shoulder).

While wandering the boardwalk near my apartment earlier today, I absent-mindedly tossed an acorn at a bench (not a euphemism, folks) and immediately doubled up in searing pain, grabbing my arm and shoulder, and plopped on the bench to wait for the pain to subside. It did…it always does.

Ill-named condition involving loss of range of motion

Ill-named condition involving loss of range of motion

But as I was getting up to finish the trip home, two cyclists stopped to make sure I was okay. They had seen me grab my arm and drop to the bench. It probably looked like a heart attack or seizure.

I explained the affliction and that the pain was mostly due to my unthinking idiocy, which seemed to allay their concerns. I thanked them, however, for checking on me and making sure I wasn’t in more serious trouble.

Nice to know that I’m never alone…I only hope I show the same concern should I be presented with something similar.

Loved the mood captured by the street lamp

Loved the mood captured by the street lamp

Talk about ALS – no bucket, no ice (video)

I’ve been trying to wrap my head around my problem with these ice bucket videos in support of ALS. Something didn’t sit right with me, and yet I felt like a complete jerk crapping on all these lovely people making loving efforts to make a difference.

And then, suddenly, it struck me. Almost none of the video efforts I have seen have included any information about ALS beyond how to spell it. They’ve done a magnificent job of raising money, but I seriously doubt that many people watching these videos have a clue as to what ALS is.

Thus, in support of their efforts and to spread not just awareness but also knowledge, I have produced a short, very homemade video (click below) with terrible production values (as in none).

I hope it helps.