
Doctors in China Lead Race to Treat Cancer by Editing Genes - troydavis
https://www.npr.org/sections/health-shots/2018/02/21/585336506/doctors-in-china-lead-race-to-treat-cancer-by-editing-genes
======
jostmey
It's fun to heap criticism on China's research. There's too many fraudulent
results, as a culture they don't value out of the box thinking, ect. That kind
of thinking hurts us, not China. But as a researcher in the US working with
data collected from Human samples, I will attest that the bottleneck to
progress are the regulations.

What we don't want are regulations that make it impossible to get the research
started. What we want are regulations that ensure that new drugs and
treatments sold on the markert actually work. This is exactly the opposite of
the situation in the US today.

~~~
amelius
Can you give some examples of regulations that are counter-productive, where
their suspension presents no ethical challenge?

~~~
ramblenode
The FDA and USDA come to mind as institutions with a lot of questionable
health policies.

"To obtain permission to market a drug, the manufacturer must satisfy the FDA
that the drug is both safe and effective. Additional testing often enhances
safety and effectiveness, but requiring a lot of testing has at least two
negative effects. First, it delays the arrival of superior drugs. During the
delay, some people who would have lived end up dying. Second, additional
testing requirements raise the costs of bringing a new drug to market; hence,
many drugs that would have been developed are not, and all the people who
would have been helped, even saved, are not.

In addition, because FDA approval is mandatory, industry and medicine must
heed FDA standards regardless of their relevance, efficiency, and
appropriateness. Not all testing is equally beneficial. The FDA apparatus
mandates testing that, in some cases, is not useful or not appropriately
designed. The case against the FDA is not that premarket testing is
unnecessary but that the costs and benefits of premarket testing would be
better evaluated and the trade-offs better navigated in a voluntary,
competitive system of drug development.

Three bodies of evidence indicate that the costs of FDA requirements exceed
the benefits. In other words, three bodies of evidence suggest that the FDA
kills and harms, on net. First, we compare pre-1962 drug approval times and
rates of drug introduction with post-1962 approval times and rates of
introduction. Second, we compare drug availability and safety in the United
States with the same in other countries. Third, we compare the relatively
unregulated market of off-label drug uses in the United States with the on-
label market. In the final section, before turning to reform options, we also
discuss the evidence showing that the costs of FDA advertising restrictions
exceed the benefits."

[http://www.fdareview.org/05_harm.php](http://www.fdareview.org/05_harm.php)

This may not be the most neutral source, but it at least raises some
interesting points.

~~~
omarforgotpwd
I doubt the FDA is a net killer of people. I'm sure many people die while
waiting for the FDA to approve new drugs but many more people would also die,
become sick, or have adverse effects if there were no standards. Furthermore
the standards the FDA sets for things you put in your body creates the
confidence that allows this market to exist in the first place. In a market
without the FDA drugs would hit the market faster and be cheaper but still
reach far fewer people because public weariness of these products would be too
high, and there would be far too many products claiming to do the same thing
making it difficult for consumers and doctors to find the most effective
treatments. Are FDA regulations 100% optimized? No, I'm sure it's a
bureaucratic nightmare. But at this point the best thing we can do is try and
further optimize these regulations -- throwing them out completely isn't
really an option.

------
lawrenceyan
There are existing immunotherapies that already target PD-1 receptors, which
is what the article’s treatment of T cells is doing ex vivo.

Pembrolizumab, for example, is an FDA approved first line therapy for all
cancers expressing high microsatellite instability or mismatch repair which is
a highly conserved attribute among people who smoke and drink, one of the main
reasons for why China has such an abnormal amount of cancer in their
population in addition to additional extraneous factors like rampant
pollution, due to their extreme carcinogenic effects.

This article seems to imply that the risk aversion taken by the FDA is
resulting in lives not being saved, but is incorrect in it’s assertions.
Especially since the utilization of CRISPR is still at a stage of, what is in
my opinion, the creation of an unnacceptable mutational burden,
immunotherapies like pembrolizumab which work to inhibit receptors through the
usage of monoclonal antibodies are the best forms of treatment. In no way do I
doubt the potential of gene editing and the good it can do, however, when I
say this. The point is though, is that when you rush things too quickly, it
inevitably ends up hurting the patient.

------
melling
"A lab at a biotech company two hours away by bullet train extracts T cells
from the blood."

Two hours away by bullet train... Something you don't hear in the US. A 21st
century infrastructure paying dividends.

~~~
refurb
Yes, because the US doesn't have any infrastructure that could support the
rapid transport of lab samples.

~~~
seanmcdirmid
This. Related, China has a huge problem with volunteer donor organ transplants
because they have no easy way to get it from the donor to donee in time (they
would have to take on a train or fly it in economy with china’s famous
aircraft delays, no helicopters or air courier services). Part of the reason
why predictable condemned prisoner donations were so important...

Now that they can’t rely on condemned prisoners anymore (at least they’ve
promised the ban is for real this time), bullet train infrastructure is quite
useful.

~~~
thinkloop
More on this in case anyone was interested:
[https://optn.transplant.hrsa.gov/resources/ethics/the-
ethics...](https://optn.transplant.hrsa.gov/resources/ethics/the-ethics-of-
organ-donation-from-condemned-prisoners/)

> prisoners be given the option of donating organs upon their death

> another suggests that condemned prisoners be offered the option of trading a
> kidney or their bone marrow in exchange for a commuted sentence of life in
> prison without parole

> Application of the death penalty is spasmodic and seemingly discriminatorily
> applied, which would suggest that these types of proposals would be coercive
> to particular classes of individuals--minorities and the poor.

There are so many things that would be sensible policy (i.e. using organs of
dead people) were it not for the surrounding hazards they create: incentive to
give death penalties, wealthy people abusing, greater chance of weak defenses,
etc.

If we could solve the slippery slope problem, so may things would be possible.

------
RestlessMind
US has become too risk averse, so every accident leads to yet another
regulation. There was a discussion on HN last year, which discussed how death
rates on public construction projects have fallen to zero (unfortunately can't
find a link to that).

On the one hand, thats a great news and I certainly don't want to be the
person to lose my life due to lax regulations. But on the other hand, we
should also consider the lost opportunity due to progress not made either due
to regulatory obstacles (like biomedical research for cancer cure discussed
here) or insufficient public funds (due to overspending on public works to
minimize fatalities).

Ultimately, the question boils down to how much dollar value we as a society
want to put on human life. A very high value will have obvious apparent
benefits but lots of non-obvious costs.

~~~
fny
It also depends heavily on whether you believe people who work in construction
(i.e. blue collar workers) are an currency expendable on behalf of people who
have cushy low risk jobs.

I’d be inclined to agree with you if we all had the same chance of risking our
lives for the greater good and we could mutually agree on what the odds should
be, but I feel like that’s why we’be come to the conclusion that it’s probably
best if people didn’t die on a construction site for the same of innovation.
(Also, I’d bet negligence is probably a more proper cause.)

Clinical trials for cancer are less fraught with the ethical problems of the
construction worker since presumably the patient is that desperate for a cure,
but we have general standards for these things like IRBs, protocols, and
physicians trained to “do no harm” just to make sure the final product is safe
and won’t guarantee a sooner death.

Also, while we may be at a disadvantage since we can’t just throw money at the
problem, we’re still making remarkable progress:
[https://ghr.nlm.nih.gov/primer/therapy/availability](https://ghr.nlm.nih.gov/primer/therapy/availability)

------
refurb
My only thought is that there is more to advancing the science than just who
starts the first trial.

------
rjett
I'm not a cellular biologist or a doctor of any kind, but I consider myself a
reasonably smart person. Reading the book Tripping Over the Truth by Travis
Christofferson and tracking the work of Thomas Seyfried and others, it makes
me think that a lot of the discussion in the battle for curing cancer is
chasing a false paradigm: that cancer is a disease of genetics and if we could
understand and edit the genome, we could cure the disease. The case for the
Metabolic theory of cancer as laid out by Seyfried is quite compelling and if
true, the implications for treatment from a patient standpoint seem to me much
more preferential than the current combination chemotherapies which are only
getting more and more expensive and only marginally more efficacious. Work on
this front is only in its infancy, but my hope is that more people become
aware, more funding directed towards metabolic therapy trials, and one day it
could at least be incorporated into the standard of care.

~~~
josu
If you read the article you'd realize that it doesn't talk about modifying the
patients DNA to cure the cancer, the are just editing T cells so they will
attack the cancer. Metabolic therapy seems promising, but I don't think it
will ever be as effective as other forms of therapy that we will come up with.

>The treatment Wu is testing involves taking a sample of blood from each
patient. A lab at a biotech company two hours away by bullet train extracts T
cells from the blood. Scientists then use CRISPR to knock out a gene in the T
cells known as PD-1. This engineering feat modifies the T cells so that they
zero in on and attack the cancer cells, once they're infused back into each
patient.

~~~
rjett
I realize the article is discussing a form of immunotherapy, but I think
immunotherapy is also in its infancy, and given the nature of cancer cells and
the heterogeneity of its own genetic makeup, immunotherapy still seems like a
very blunt weapon in the war on cancer. For a patient who has already been
beaten down by rounds of chemo and radiation, it offers a last ditch hope for
survival, but its still laden with risks and adverse outcomes.

On the contrast, metabolic treatment is tough from the standpoint that it
requires strict discipline by the patient to adhere to the protocol, but the
"side effects" may actually enhance overall health at the cellular level. It's
a treatment that at the very least could be melded with the current standard
of care to achieve better outcomes, and yet there's very little awareness of
it, possibly because there's not a lot of money in it for hospital systems.

------
perseusprime11
It will be interesting to see how long it takes to cure this disease given the
incentive of pharmacy companies making money on drugs.

~~~
lopmotr
I don't think that's really an obstacle. New biotech companies form all the
time to try and bring new tech to market. They get zero money from any
existing drugs.

------
yohann305
Cancer treatment should not be viewed as a race. The world needs to team up.
We all win when someone finds a new cure.

~~~
loceng
Races can be healthy - non-aggressive in nature - like racing for prestige;
you can race other people on your own team too! Sharing information of course
is important in case important discoveries are kept quiet by a corporation
with ulterior motive.

~~~
_rpd
I would go even further and say that competition is vital to innovation.
Without it, too few are willing to take risks and progress stagnates.

~~~
IntronExon
You don’t think the prospect of treating _cancer_ is insufficient motivation,
there needs to be some poxy “race” as well? You’re selling both the
motivations of researchers, and the practical rewards of that research short.

~~~
jamesrcole
What is the problem with there being a race element as well?

Anyway, I don't see how it's avoidable. There'll be kudos, prestige, more
grant money, etc for people who make advances, so there's going to be a race
element to it as well.

~~~
da_chicken
> What is the problem with there being a race element as well?

What about competition makes it some universal good? The entire field of game
theory exists because direct competition creates paradoxes and dilemmas, and
_cooperation_ can result in greater rewards for everyone involved.

More specifically, doesn't anybody else remember the numerous scientific
misconduct scandals that have plagued China? In their race to be first they've
been willing to sacrifice research integrity to get there. When we see 40% of
biomedical papers from China having problems
([http://retractionwatch.com/2017/05/18/four-10-biomedical-
pap...](http://retractionwatch.com/2017/05/18/four-10-biomedical-papers-
tainted-misconduct-chinese-scientists-say/)) I'm not entirely sure I'd trust
their result claims.

~~~
jamesrcole
> What about competition makes it some universal good?

You're criticising a strawman. Nobody said it was a universal good.

I said it was unavoidable (it is intrinsic to the research process), and I
said (in various comments) that it's a good thing (i.e. a net positive),
including that there's clear historical evidence of this.

~~~
da_chicken
> I said it was unavoidable (it is intrinsic to the research process)

No, it isn't. It's intrinsic to our research _culture_ and that's wildly
different.

Look, competition gets us things like Microsoft Windows and iOS. Cooperation
gets us things like BSD and Linux. Competition gets us the Google Play App
store. Cooperation gets us the Debian repository.

> and I said (in various comments) that it's a good thing (i.e. a net
> positive), including that there's clear historical evidence of this.

Except you don't cite anything.

What about the fact that essentially nobody does repeat experiments because
they're all busy racing for original research?
([https://en.wikipedia.org/wiki/Replication_crisis](https://en.wikipedia.org/wiki/Replication_crisis))
What about the fact that people often select studies based on what will
attraction attention, rather than what will actually best advance the field.
Boring and uninteresting but extremely important research topics get ignored
because they don't result in glory for the university or researcher. We're
emphasizing the importance of breakthroughs over incremental research while
simultaneously not reproducing those studies to confirm their findings!

 _That_ is how a culture of competition over cooperation in research and
science harms our ability to solve problems and conduct research.

~~~
majormajor
> Look, competition gets us things like Microsoft Windows and iOS. Cooperation
> gets us things like BSD and Linux. Competition gets us the Google Play App
> store. Cooperation gets us the Debian repository.

So first, which of those two competitors, BSD and Linux, was the wasted
effort, then?

And, using Macs, Windows, and Linux all on a regular basis: based on that
example I can't help but be fairly pro-competition. Windows is a far smoother
experience to set up than Linux. Photoshop and Lightroom beat the hell out of
Gimp/Darktable/Krita/whatever. Office similarly doesn't really have effective
competitors. Those things all got good through competitive pressure, having to
beat out the alternatives in order to be good enough for people to pay for.

We can't predict the future, what paths will be useful and what ones won't,
well enough to scrap it.

Competition has its downsides and has to be corralled, but cooperation can
lead to waste just as easily. Groupthink. Missed opportunities. Unexplored
areas in the solution space because we guess wrong.

------
vadimberman
Now with numbers and without comments from European anthropologists in
Singapore: [https://qz.com/1185488/chinese-scientists-used-crispr-
gene-e...](https://qz.com/1185488/chinese-scientists-used-crispr-gene-editing-
on-86-human-patients/) .

Spoiler alert: I wouldn't want any other country to follow the example of
China. Sometimes, human lives are more important than KPIs and being first...

Some interesting parts:

> The Chinese ministry of health has to approve all gene-therapy clinical
> trials in China, but these regulations appear relatively relaxed.
> __According to the WSJ, at Hangzhou Cancer Hospital, for example, a proposal
> to test a cancer treatment that modifies patients’ immune cells was approved
> in a single afternoon. __One member of the hospital’s approval committee
> told the WSJ that she did not really understand the science laid out for her
> in a 100-page document, but was told that the side effects were mild. This
> was enough for her to give it the go-ahead.

...

> China is taking the lead in the global race to perfect gene therapies.

> Scientists have genetically engineered the cells of at least 86 cancer and
> HIV patients in the country using Crispr-Cas9 technology since 2015, the
> Wall Street Journal reports (paywall). Although no formal scientific papers
> have been written about these experiments, doctors told journalists at the
> WSJ that some patients have improved. There have also been least 15 deaths,
> seven of which were in one trial.

86 (!!!) patients.

