Is Bill Nye really helping science?

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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.

 

THE NIGHT BEFORE DEFENSE (or A Visit From Citrate)

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Twas the night before Defense, when all through the lab

Not a gel box was shaking, with stain or with MAb;

The columns were hung in the cold room with care,

In hopes that my protein, I soon could prepare;

 

The post-docs were nestled all smug in their beds,

While extracts of barlied hops muddled their heads;

With the tech in the suburbs and PI the same,

I had just settled down to another video game.

 

When out of the fridge there arose such a clatter

I sprang from the terminal to see what was the matter.

Away to the cold box, I flew like a flash

But the stench was o’erpowering and I threw up beef hash.

 

The mould on the dampest of walls which were cold

Had the softness of kittens only seven weeks old;

When what to my view, a thing I despise

But a half-eaten sandwich and four tiny mice;

 

With a little old scientist, so lively and galling,

I knew at a glance, it was Linus Pauling.

More vapid than undergrads, his charges they came,

And he whistled, and shouted, and called them rude names.

 

“Now, Watson! Now Francis! You strange little modellers!

On Luria! On Bertani! You stupid old broth’lers!

To the top of the bench, to the top of the wall!

Purify! Purify! Purify all!”

 

As dry heaves before the committee meeting, bend

A young student’s body and his colon distend,

So up to their earlobes, acytes they grew,

With a sack full of antibodies, their skin turning blue.

 

And then, for a second, I heard from the ‘fuge,

An unbalanced rotor spinning something too huge.

Where I put down my hand, to better hear the sound,

Came the snapping of sparks from a wire sans ground.

 

Pauling’s hair was all wavy, and I thought I must be sick

`Cause the curl in his hair looked just like a helix.

On an arm load of oranges, he started to snack

Recalling his fetish with ascorbate, the quack.

 

His eyes were all wrinkled, but the cheeks were yet red;

Not too shabby for a man who was several years dead;

The leer of his smile was just a tad scary

And the snow on his rooftop made his head yet quite hairy;

 

The end of a pipette, he held in his teeth

And a pile of kimwipes lay around his big feet.

He held a small vial of something quite gel-ly,

A mercaptan no doubt, for it make him quite smelly.

 

He changed `round the columns, adding to the confusion

And I laughed to spite my own paranoid delusion.

A wink of his eye and a rotation of his head,

Told me whatever I drank would soon leave me dead.

 

He spoke not a word, just buggered up my work,

And dried all my resins, that silly old jerk.

And separating his middle finger from first, fourth and third,

That crazy, old bugger, just flipped me the bird.

 

He grabbed up his cohorts and ran down the hall,

And away they all flew, letting me take the fall.

That is why, dear Committee, I am sorry to say,

I need a five year extension, starting today.

Let go(al) and let…just let go

Mountain

Don’t have to climb the mountain to admire its beauty

Where do you see yourself in five years?

It’s a common question at job interviews and often creeps in silently when people reach age or career milestones.

Rephrased more broadly, it is asking: What are your goals?

In most Western societies—the only ones I really know—we are told it is good to have goals; that you need to set your sights on a destination and follow that path to its conclusion. It is how you get ahead. It is how you find happiness, or at least the stuff that brings happiness.

I have spent my life working this way.

Checklist

Life goals complete

I tell you this not to present my resume—you can find that on my LinkedIn pages (yeah, I have two)—but rather to explain the pattern of my life (and probably yours) in contrast to where I am today.

You see, for the first time in my life, I have no goals. And I am finding it incredibly disconcerting.

Sure, like everyone else, I have daily, weekly, monthly and yearly obligations.

I need money to pay for rent, food, bills, hockey tickets, beer. I have editorial deadlines and the odd gift to buy. But I have no long-term goals. I am living my life without my next destination in mind.

Five years from now? Hell, I sometimes don’t know where I’ll be five minutes from now.

In some ways, I am as close to living in the moment as you can get without living under a tree or in a cave (basement apartment notwithstanding). And it’s freaking me out.

Having a goal is a hard habit to break after 50+ years.

Butterfly

What if I had missed this moment?

To be clear, I’m not looking for a goal—floating freely has some lovely benefits—but I struggle some days to know what the point of my day is or was.

Simply being is really simple—it requires no preparation or gear—but our society has taught us that it is wasteful; that it is selfish; that even our “free” time must be productive.

Having no goals, I find, is entirely selfish. I can only affect change in myself.

But I’ve come to realize that “selfish” isn’t bad in and of itself; only when it negatively impacts others, which I don’t believe I am.

Still, like a good Pavlovian pound puppy, I sometimes find myself whimpering at the window, waiting for someone to throw the stick of destiny, to give my life meaning and purpose.

Is it okay or desirable to lead a purpose-less life? Is that my purpose? [Never met-a-physics that didn’t hurt my brain.]

But then, it’s 7:30 a.m. and the alarm goes off. I turn it off and go back to sleep.

Life without goals definitely has its upside.

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

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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.

12 Days of Gratitude – Alayna

Alayna

This is my friend Alayna. For every reason that I told you Ned was a good man, Alayna defines what it is to be a good woman.

Friend, mother, wife, educator, nut-bar, science nerd: all qualities that make Alayna a very special woman, someone who blesses my life with every witticism and wise-crack. Buried behind a veneer of sarcasm is a passionate soul who is both demanding of and deeply dedicated to others.

To know Alayna is to have your life enriched, your mind expanded and your passions empowered (and sometimes your ass kicked).

 

(Part Ten of my 12 Days of Gratitude…because the rest of the news sucks)