A Woman Who Stood Between America and a Generation of ‘Thalidomide Babies’

https://www.smithsonianmag.com/science-nature/woman-who-stood-between-america-and-epidemic-birth-defects-180963165/

by dcminter • 5 years ago

156 105 5 years ago

This explains about everything you need to know about the ethos of the FDA. It’s baked in at a really foundational level.

As a biomedical person, i find the FDAs policies and procedures eminently sensible, perhaps especially when they chafe, and this is why.

I do not envy them their jobs even the littlest bit, but I’m glad they’re around.

k__• 5 years ago

How come, the US has an opiate crisis?

meekrohprocess2• 5 years ago

Many American regulatory institutions have crumbled in the past few decades, the FAA being a particularly jarring example.

In some cases it seems like peoples' trust in those regulators may be fueled by nostalgia, but the FDA does seem like one of the few agencies that has retained some measure of independence.

Looking at what has happened in this nation's other industries and institutions, only one crippling decades-long medical crisis doesn't seem all that bad.

formerly_proven• 5 years ago

A while ago I posed a similar question and the answers/downvotes made it clear to me why; Americans have a broken model of pain management. Americans think that opiates are necessary to manage the pain from most surgeries, back pain, headaches etc., so, they get opiates to do that, with the obvious and foreseeable catastrophic consequences.

every• 5 years ago

Regulatory capture can be a significant factor:

https://en.wikipedia.org/wiki/Regulatory_capture

xxpor2• 5 years ago

That's sort of a different situation. Thalidomide did what it was supposed to, but ended up having horrible unknown (at the time) side effects. The FDA correctly didn't approve it based on the lack of safety data.

Opiates also do what they're supposed to, but the fact that they're addictive wasn't a mystery. They're safe if taken and prescribed as instructed. The failure is more on the DEA and other enforcement bodies for not dealing with the obvious prescription abuse. The FDA doesn't make controlled substance decisions.

Scoundreller• 5 years ago

The FDA only protects you against novel drugs.

Once something is approved for something (or grandfathered!), it’s a free-for-all for prescribing and usually insurance coverage.

mhh__• 5 years ago

The FDA doesn't do that kind of regulation if I have read up on it correctly.

That and opiates do what they say on the tin - it's more of a policy problem than a specific thing you can just FDA-away.

freeflight• 5 years ago

That has way more to do with ease of access, due to over-prescription practices resulting from pharma lobbying, than FDA med approval.

rscho8• 5 years ago

The US opiate crisis has its roots deep in US healthcare culture and the blame lies on both sides of the doctor-patient fence. US docs used to prescribe opiates like candies, but US patients expect to feel no pain at all and are extremely aggressive legally speaking. Those two aspects go hand in hand.

My 2c.

hilbert429• 5 years ago

Exactly, the FDA was not only completely incompetent but indirectly responsible for the deaths of thousands. It should have pounced on Purdue at the very outset.

Unlike much medical/drug research, knowledge about opioids and opioid addiction is well known.

The FDA irresponsibly failed to act on a no-brainer.

orangecat• 5 years ago

On the other hand, it's likely that thousands of people will die due to the delay in approving the AstraZeneca vaccine. There are always tradeoffs, and it's not at all clear that the FDA is operating at the optimal level of caution.

ghaff3• 5 years ago

It's also very easy, especially at the moment and with the benefit of hindsight, for people to be going that the FDA last March should have said "F it. Go out with whatever vaccines you think will work and see how it goes." Which is what a fair number of people believe (at least other than those who still feel testing was rushed).

Aerroon• 5 years ago

My thinking on this was the exact opposite. Emergencies like this are precisely when you need these types of agencies the most, because you're talking about treatments that will be taken by a huge amount of people in a short timespan. Negative effects from treatment could end up as a catastrophe on their own. It's more important than ever to get it right.

est31• 5 years ago

I guess it depends on the danger of the virus. If the virus is as congagious as covid for example, but it kills 40% of people even among the young, there would be far less concerns about giving experimental vaccines to healthy people. I hope the vaccine production lines we are building now will stay well oiled until the inevitable hit of the next pandemic.

foobiekr• 5 years ago

Well.. Thalidomide - in pregnancy - was replacing diethylstilbestrol, which was still in use in the US until 1971.

rscho8• 5 years ago

Yes, but cancer is much less spectacular than missing limbs. Especially when it occurs years later in the next generation.

refurb5• 5 years ago

No. Those two drugs were used for different things.

ggreer4• 5 years ago

In total, Thalidomide caused around 2,000 deaths and 10,000 birth defects. Compare that to the 100,000 people that the FDA killed by not approving a single beta blocker sooner. The FDA waited until 1981 to let doctors prescribe Timolol to prevent heart attacks. Stunningly, the FDA bragged that approving Timolol would save up to 17,000 lives a year.[1] That same drug had been in use in Europe since the mid-70s, meaning that the FDA tacitly admitted to killing 100,000 people by forbidding its use in the US. Even the original beta blocker (propranolol) wasn't allowed to be used for angina or hypertension until 1978, 13 years after it had been approved in Europe. That delay likely killed more than 100,000 people.

The FDA is also the reason why epi-pens are so expensive[2], why Martin Shkreli was able to jack up the price of Daraprim[3], why many drugs suffer from shortages[4], and why home testing for covid was delayed for so long[5]. And don't forget that covid community spread was discovered in February of 2020 only because researchers risked jail time by violating the FDA's prohibition on testing.[6]

Yes, the FDA lets leaders avoid an occasional political snafu. But the organization kills far more people than it saves.

1. https://www.washingtonpost.com/archive/politics/1981/11/26/d...

2. https://slatestarcodex.com/2016/08/29/reverse-voxsplaining-d...

3. https://slatestarcodex.com/2015/09/24/the-problems-with-gene...

4. https://slatestarcodex.com/2019/04/30/buspirone-shortage-in-...

5. https://www.nytimes.com/2020/05/15/us/coronavirus-testing-se...

6. https://www.nytimes.com/2020/03/10/us/coronavirus-testing-de...

hprotagonist3• 5 years ago

So, defensive language aside, I think that the FDA has a point in its white paper. The reason we don’t have cures for a lot of diseases is not so much that pesky regulations keep great drugs from getting to the market. It’s that we don’t know enough – yep, even in 2015 – to make so many great drugs.

https://blogs.sciencemag.org/pipeline/archives/2015/08/07/on...

Now, when I mentioned that we’d surely have killed off more people by doing drug research by the more direct routes, the reply is that we’ve been killing people off by moving too slowly as well. That’s a valid argument. But under the current system, we choose to have people die passively, through mechanisms of disease that are already operating, while under the full-speed-ahead approaches, we might lower that number by instead killing off some others in a more active manner. It’s typically human of us to choose the former strategy. The big questions are how many people would die in each category as we moved up and down the range between the two extremes, and what level of each casualty count we’d find “acceptable”.

So while it’s not crazy to say that we should be less risk-averse, I think it is silly to say that the FDA is the only (or even main) thing holding us back. I think that this has a tendency to bring on both unnecessary anger directed at the agency, and raise unfulfillable hopes in regards to what the industry can do in the near term. Neither of those seem useful to me.

https://blogs.sciencemag.org/pipeline/archives/2013/08/19/is...

The replies to my comment here nicely delimit the cleft stick the FDA is in. You are on the "oh, god, just let them try it already! the FDA are stick in the mud beancounters just holding everyone back" side.

A few others are on the "But this one time, they didn't pull Vioxx fast enough, and look at what it got us!!" side.

For myself, I'm glad that 1. i don't have to walk that tightrope and 2. there are enough people to make an institution old enough to have memory that _do_ walk that tightrope.

But i'm pretty sure that sanity is somewhere in the middle, case by case, agonizingly slow clinical trial by agonizingly slow clinical trial.

refurb5• 5 years ago

Your timolol example is not that convincing.

The article you reference mentions a major Norwegian study showing that it prevents death had just concluded. So the FDA was acting on fresh data.

In addition, timolol is one of many molecules in the beta-blocker class and propranolol, another beta-blocker, was already approved in the US since 1973. And from a quick cursory google search, it appears there is no difference between the two when it comes to reducing hypertension and future risk of heart attacks.

hilbert429• 5 years ago

"Even the original beta blocker (propranolol) wasn't allowed to be used for angina or hypertension until 1978, 13 years after it had been approved in Europe. That delay likely killed more than 100,000 people."

I was unaware that propranolol was approved as late as that in the US. This seems very strange as Sir James Black's work on propranolol was widely known and he was widely respected before he was knighted and awarded the Nobel Prize for his work with both propranolol and cimetidine.

https://en.wikipedia.org/wiki/James_W._Black

Why on earth did the FDA take so long to approve it given that there was no other beta blocker available at the time? (Thus, the hypertension issue could easily have been perceived as a crisis even allowing propranolol to be, say, approved on a temporary basis much earlier on.)

Looking at the FDA's record of approvals, it's hard to see any consistent granularity in its approach. I'm curious as to why this may be the case.

refurb5• 5 years ago

As someone who works in the healthcare industry I agree. I think the FDA does a very good job all things considered. They have approved drugs that were desperately needed (Avastin for breast cancer) based on little evidence, only to later pull them when the data didn’t support approval. They appropriately balance risk versus benefit.

And there is more at stake than most people realize. Approve a vaccine that isn’t safe and people will lose trust in general and will refuse any vaccine. Then what?

Lots of Monday morning armchair drug regulators in this thread.

mchusma• 5 years ago

I think your position, and that of the FDA is based on emotion, and not any logical reasoning.

The Thalidomide crisis cased a few thousand issues.

The risk-benefit analysis clearly favored lifting the ban on COVID vaccines after successful phase 1 trials, in June 2020 or so. They decided they should be banned until further study, during a pandemic.

The FDA was empowered explicitly by congress to take more aggressive action during such a time. They opted instead to ignore that mandate, and instead run things like normal, albeit with taking reasonable time to respond to a crisis. The deaths of 100,000 to 400,000 could be directly blamed on the simple fact that for most of this crisis, we had not 1 but approximately 8 vaccines that were all expected to be safe and work, and all turned out to be safe and to work. Vaccines candidates are not like Thalidomide, period.

It's important for citizens to publically shame the FDA for their actions, and demand change from our elected officials.

mattkrause2• 5 years ago

It’s simply not true that all of the candidate vaccines worked.

- The Sanofi-GSK one produced meh immune responses in the elderly, which is the population most at risk. (https://www.cbc.ca/news/health/sanofi-gsk-vaccine-covid19-tr...)

- Merck/MSD abandoned TWO candidates, V590 and V591. https://www.merck.com/news/merck-discontinues-development-of...

- CSL/Queensland abandoned theirs because it interfered with HIV tests. https://www.csl.com/news/2020/20201211-update-on-the-univers...

hilbert429• 5 years ago

"...i find the FDAs policies and procedures eminently sensible..."

Damn shame the FDA was asleep at the wheel during the opioid epidemic! (It's a shame you've not bothered to justify that statement in the light of overwhelming evidence to the contrary.)

The FDA did SFA to stop Purdue Pharma selling—sorry—pushing boxes of OxyContin to all and sundry as if they were kids lollipops despite the fact that it would have been aware of over a hundred or more years of solid medical evidence of the dangers of narcotics and narcotic addiction. The fact that any opioid narcotic that's capable of killing pain is addictive—and if not very carefully managed—very addictive is 101 medical/pharmacy knowledge. Even kids know the fact!

Armed with this knowledge the FDA knew what Purdue was doing was completely unacceptable, so why didn't it act?

https://www.theguardian.com/us-news/2019/jan/24/fda-opioids-...

The FDA still has a lot to answer for its negligence over the Purdue/Opioid crisis. Its ethics are nothing like they were in Frances Kelsey's day.

—

Later edit: Let me add Frances Kelsey was a true hero, she saved many kids from developing terrible deformities! Despite current criticism of the FDA by many including myself, we should never forget her contribution to medicine.

thereare5lights• 5 years ago

Racism played a part in this too

If a doctor subscribes to stereotypes of what an addict looks like — nonwhite, from a low-income community — the physician may assume their white, middle-class patients are immune to addiction, he says.

https://www.wbur.org/hereandnow/2020/01/03/bias-opioid-presc...

roenxi• 5 years ago

From a "well what did you expect" perspective - delaying drugs and asking for more safety data is occasionally going to result in scary drugs getting caught and kept off the market.

The problem is the flip side - when wonder drugs are delayed causing unnecessary pain and suffering - generates no human interest stories. The damage of increasing cost of drugs and delaying the rate of improvement because of delays in the approval process is also an unknown.

The FDA is a process - every time something goes wrong, bureaucrats take heat and then tighten the standards. This process is going to be more conservative about approving drugs than is rational.

marton78• 5 years ago

As a European who had to deal with getting a medical devices approved both in the EU and in the US: mad respect for the FDA.

There is lots of paperwork required on both sides, but the difference is who accompanies the project. In the EU it's bureaucracts with zero domain knowledge, in the US it's domain experts who asked the right questions and were strict, but also genuinely helpful.

CryptoPunk• 5 years ago

These are problems that would have been solved without the preemptive FDA ban on unapproved drugs.

Society, as usual, over-reacted, and created a set of highly restrictive rules that have cost probably millions of lives over the subsequent decades.

A much more sensible law in the aftermath of the drug scandals of the 1930s and 40s, that would have run a much much lower risk of having a myriad negative consequences, would have been a requirement to include on any drug, a disclosure of whether it is approved by the FDA. Non-approved drugs could have been required to include a warning that the FDA recommends a person not take the drug as it has not been verified to be effective or safe.

This provides most of the benefits of the FDA's role as gatekeeper, without most of the harm done by heavily restricting a market and making it totally dependent on a single central authority. Providing consumers with the ability to ignore the warnings of the FDA would have acted as a lifeline/failsafe in cases where the FDA erred.

ficklepickle• 5 years ago

While this is great and all, the comments indicate that tons of doses circulated the USA as samples. There are two people in the comments claiming to be survivors from these samples.

If this is true, then the article is incorrect. It appears that Americans were just denied compensation because the drug wasn't approved.

I'm sure the harm would have been much greater had the FDA approved the medication. But it seems unfair to say they were no victims in the USA.

xiphias2• 5 years ago

The article reports that there were victims. Are we reading the same article?

potiuper• 5 years ago

The title of the page implies there were no victims; there was "A Generation of 'Thalidomide Babies'" in the U.S. even though greatly limited.

dcminter• 5 years ago

The article itself states that samples were distributed and that "In the U.S., 17 cases of congenital deformities were reported"

LatteLazy• 5 years ago

From the Wikipedia article:

At the time of the drug's development, scientists did not believe any drug taken by a pregnant woman could pass across the placental barrier and harm the developing fetus

https://en.wikipedia.org/wiki/Thalidomide

Wtf?

burlesona• 5 years ago

I mean, people think all kinds of things that seem plausible at the time and look crazy in hindsight to future generations. This is what progress looks like.

rscho8• 5 years ago

Medicine used to be, and in substantial part still is, a disordered heap of hypotheses relying on practical experience and relayed by the stars of the field. There are plenty of strange examples throughout history. For example, we used to believe until not so long ago that infants couldn't feel pain (with all the 'interesting' consequences on practice you can imagine).

myself248• 5 years ago

I'm less than convinced that anyone sincerely believed that. It seems more plausible that it's a lie they told themselves to paper over other cultural, profit, or institutional pressure.

jcranmer• 5 years ago

It's not an entirely crazy concept. There are several barriers in the body that isolate systems from one another that can be challenging to cross, and the blood-brain barrier is probably the most difficult of all of them. The existence of the blood-brain barrier has been known since the early 20th century (despite the difficulty of actually finding it!), and it wouldn't be entirely crazy to a priori believe that the placental barrier would be similarly strong. As it turns out though, the placental barrier is probably the weakest such barrier.

blahedo• 5 years ago

the placental barrier is probably the weakest such barrier

At least, in humans (and other primates and rodents, but not most mammals). Human embryos/fetuses receive more nourishment and achieve more growth during prenatal development in part because the placenta invades the uterine wall much more—for lack of a better word—parasitically than in other mammalian species. That's great for a lot of developmental stuff for the fetus, but it does make transfer of (say) drugs considerably easier. (It also is the source of a lot of the common maternal complications in human pregnancy and is the reason one should at least be in contact with medical doctors while pregnant, even if a low-intervention or home birth plan is intended....)

chosen1111• 5 years ago

I wonder what names she was called at the time for her refusal to go along with the established research from the pharmaceutical and medical community

tomcam• 5 years ago

Thalidomide babies were my age and not unknown where I grew up. Limb deformities differed: sometimes they had flipper-like appendages, sometimes shortened limbs. (FWIW while cruelty was extremely common back then I never saw a single case of anyone handicapped being made fun of. Nor did I ever witness any racist behavior in my racially integrated neighborhood.)

There was a locally famous dude at the public pool who was kind of the coolest guy around. His legs stopped at knee length and he would pull himself up the high dive ladder, walk on his hands to the end of the diving board, and casually launch himself off the end perfectly every time. It was spectacular.

WalterBright5• 5 years ago

On the other hand, there are costs with delaying approval. This is pretty obvious with the Covid vaccines, probably at least 200,000 on the dead side of the ledger.

Another cost that's harder to quantify is the cost in lives and misery of drugs never developed because it's for an uncommon and there's no way to make back the money needed to pay for FDA approval.

ip263• 5 years ago

There are like 50+ COVID vaccines in development. Which one do you administer? Forget about side effects, half of them are probably duds! Can we afford to administer billions of vaccines that don’t even work?

WalterBright5• 5 years ago

With the agonizingly slow rollout of the current vaccine, we wouldn't be administering billions of vaccines without soon finding out if it is efficacious or not.

Can we afford

Evidently we can afford to spend several trillion dollars and hundreds of thousands of deaths waiting 6 months for the vaccine trials.

JoshuaDavid• 5 years ago

Yes? 10 billion vaccine doses that cost $100 each would be a trillion dollars. Which is somewhere between 7% and 25% of the total cost of COVID-19 to the US.

The real question is whether we can afford to use our non-emergency drug approval process in a time of crisis. This time the answer is probably "yes, and it probably only cost a few tens of thousands of lives and a few trillion dollars" but if the disease in question had been Ebola instead of COVID I worry that we would have seen the same ineffective response that optimizes for minimizing liability instead of maximizing effectiveness.

voldacar• 5 years ago

Can we afford to administer billions of vaccines that don’t even work?

the seen and the unseen strikes again

We have already sacrificed trillions of dollars in shutting down or greatly restricting the global economy for a year, so any questions of "can we afford" are totally moot by now

xyzelement• 5 years ago

I love stories of people thoughtfully doing their jobs and having huge life saving impact like this.

I was saying to my wife on a recent drive, that there's some civil engineer somewhere who figured out you can embed those little light reflectors into highway lane markets, and some other engineer who figured out those perpendicular cuts in the asphalt that vibrate your car before you run off the road.

Both of these probably naturally arose in the context of their work, and both of these things passively save hundreds of lives daily.

Stratoscope• 5 years ago

For the curious:

https://en.wikipedia.org/wiki/Botts%27_dots (named after Elbert Dysart Botts)

https://en.wikipedia.org/wiki/Raised_pavement_marker

https://en.wikipedia.org/wiki/Rumble_strip

dingsbumps• 5 years ago

I recently listened to an interesting episode about those reflectors on the 99 Percent Invisible podcast. This [1] is an associated article on their site that seems to have similar content to the episode I listened to.

[1] https://99percentinvisible.org/article/decoding-cats-eyes-gl...

chefkoch• 5 years ago

And now Thalidomide is used in treating cancer and sold for over $200 a pill. Quite a nice markup for telling the patients not to get pregnant while on treatment.

madaxe_again• 5 years ago

Only one enantiomer caused birth defects - and a defect in the original manufacturing process created L- as well as D- chiral species. Pretty sure it no longer contains the problem enantiomer.

Metacelsus• 5 years ago

The enantiomers can interconvert (racemize) within the body, so it's not that simple.

eterm• 5 years ago

It needn't cost that much, the UK's NHS is charged around $15/pill if I'm reading this right: https://bnf.nice.org.uk/medicinal-forms/thalidomide.html

Also worth noting that "Don't get pregnant" also extends to "don't get anyone else pregnant" since the side effects can pass from men to women too.

nojvek• 5 years ago

Also reminds me how people were blaming for FDA for vaccine delays including President Trump.

It’s not a vaccine, until it’s proven safe. While FDA isn’t perfect they have stringent procedures to prove something is safe.

The way FAA let Boeing ship planes that killed people, and lost their trust, same applies to FDA. If people die and have irreversible damage, it’s on their hands.

A Woman Who Stood Between America and a Generation of ‘Thalidomide Babies’

Related Stories