On the face of it it sounds like the nice narrative we are fed every time something like this happens. I haven’t been following the international scene, and frankly it wouldn’t even surprise me if Europe headed for nativism and blood-related nationality. It is what is at the basis of their nation states (even if it’s often a lie. For instance I’d hazard that a lot of people in Portugal — yes, d*mn it, I’ll do the DNA testing. Let the house sell and let me have some money first — are as mixed as Americans. My kids call Portugal the reservoir tip at the end of Europe, which is unkind but somewhat accurate since that portion of land was part of the Celtic commonwealth, before being invaded by Carthaginians, Greeks, Romans, Germanic tribes, Moors (though their contribution in the North is minimal as the North was usually administered by overseers with little or no actual colonization) French crusaders, Viking raiders. Then there were British and Irish merchants due to ties going back before the Carthaginians who would set up trading posts, send their younger sons over, sometimes engage in a bit of raiding, etc. There are unkind proverbs about blue eyed Portuguese, but there are also a lot of them. (Two of my grandparents. A third was green eyed.) And in the end sometimes I think all of us are the result of some girl who tripped (on purpose or not) while evading a foreigner. All this to say that when my dad talks of the “The Portuguese Race” (and boy, does he) he’s mostly talking of a mythical entity. But it’s one they all believe in as hard as they can.)
Sarah A. Hoyt, “Multiculturalism IS Racism”, According to Hoyt, 2015-04-04.
May 15, 2015
April 22, 2015
Rosie Cima looks at the complex relationship between humans and dogs … dog breeds, that is:
Meet the Skye terrier. Named after the Scottish Isle of Skye, he’s one of the oldest terriers in the world — with a lineage tracing back to the Middle Ages. He’s also been a very popular dog in his day. Queen Victoria kept several as pets starting a fashion trend. Mary, Queen of Scots kept one, which hid under her skirt at her execution. Famously loyal, “plucky but dignified”, and an important cultural icon, this is the kind of dog people erect statues of. In fact, they have.
Want one? Better act fast: the breed could go extinct in your lifetime.
Skye terrier breeders are doing their best to change the tide, but things don’t look good. The global population is between 3,500 and 4,000, making the once-common breed one of the rarest in the world. Skye terriers are rarer than red pandas. In the UK, there were only 17 puppies of the Skye terrier breed registered in 2013. Breeders say they need 300 births a year to maintain a healthy population and avoid complications from inbreeding.
How did this happen?
For most of human/canine history, dog breeds evolved gradually, alongside human society, to fill different functional roles as they were needed. If a society or economy shifted, and the role was no longer needed, the breed ceased to exist. Those dogs were either bred for a different purpose or were subsumed into the general dog population.
April 3, 2015
Alex B. Berezow makes a case for the venerable New York Times to not cover science stories:
What has gone so wrong for the NYT? Many things are to blame. The paper’s leftish editorial page is out of step with a large portion of the American public. A high-profile scandal, in which journalist Jayson Blair was caught fabricating articles, damaged its credibility. The biggest factor, however, is the rise of credible challengers — both print and digital — that simply do better journalism. There is little incentive to spend money to read the NYT when superior news coverage (and more sensible editorializing) can be found elsewhere.
The NYT‘s science coverage is particularly galling. While the paper does employ a staff of decent journalists (including several excellent writers, such as Carl Zimmer and John Tierney), its overall science coverage is trite. Other outlets cover the same stories (and many more), in ways that are both more in-depth and more interesting. (They are also usually free to read.) Worst of all, too much of NYT‘s science journalism is egregiously wrong.
Reliance on fringe, pseudoscientific sources has become something of a trend at the NYT. Its most deplorable reportage involves the science of food, particularly GMOs. Henry Miller, the former founding director of the FDA’s Office of Biotechnology, reprimands anti-GMO foodie Mark Bittman for “journalistic sloppiness” and “negligence” in his “[inability] to find reliable sources.”
Furthermore, in a damning exposé, Jon Entine reveals that Michael Pollan, a food activist and frequent NYT contributor, “has a history of promoting discredited studies and alarmist claims about GMOs.” Even worse, Mr. Entine writes that Mr. Pollan “candidly says he manipulated the credulous editors at the New York Times… by presenting only one side of food and agriculture stories.” Mr. Pollan was also chided by plant scientist Steve Savage for disseminating inaccurate information on potato agriculture and fearmongering about McDonald’s French fries.
On many matters concerning nutrition or health, the NYT endorses the unscientific side of the debate. For instance, The Atlantic criticized a New York Times Magazine essay on the supposed toxicity of sugar. At Science 2.0, Hank Campbell mocked an NYT writer’s endorsement of gluten-free diets, and chemist Josh Bloom dismantled a painfully inaccurate editorial on painkillers.
March 20, 2015
Epigenetic researchers – “We can double the size of these bugs!” Everyone else – “No, thanks. We’re good.”
Science can be a great source of fascinating experiments. Doubling the size of insects is perhaps not the best way to advertise your particular speciality, however:
Researchers have changed the size of a handful of Florida ants by chemically modifying their DNA, rather than by changing its encoded information. The work is the latest advance from a field known as epigenetics and may help explain how the insects — despite their high degree of genetic similarity — grow into the different varieties of workers needed in a colony.
This discovery “takes the field leaps and bounds forward,” says entomologist Andrew Suarez of the University of Illinois, Urbana-Champaign, who wasn’t connected to the study. “It’s providing a better understanding of how genes interact with the environment to generate diversity.”
Ant nests have division of labor down pat. The queen spends her time pumping out eggs, and the workers, which are genetically similar sisters, perform all the other jobs necessary to keep the colony thriving, such as tending the young, gathering food, and excavating tunnels. Workers in many ant species specialize even further, forming so-called subcastes that look different and have different roles. In Florida carpenter ants (Camponotus floridanus), for example, workers tend to fall into two groups. Minor workers, which can be less than 6 mm long, rear the young and forage for food. Major workers, which can be almost twice as long, use their large jaws to protect the colony from predators.
A team from McGill University in Montreal, Canada, suspected that the mechanism involves DNA methylation: the addition of a chemical to DNA. Genome sequencing and other methods suggest that these physical differences don’t usually stem from genetic differences between individual ants. Instead, environmental factors help push workers to become majors or minors — specifically, the amount of food and coddling that young ants receive. But just how do these factors change the size of ants?
February 20, 2015
In Nature, Claire Ainsworth explains why it’s becoming more difficult to discuss sex as a binary:
Sex can be much more complicated than it at first seems. According to the simple scenario, the presence or absence of a Y chromosome is what counts: with it, you are male, and without it, you are female. But doctors have long known that some people straddle the boundary — their sex chromosomes say one thing, but their gonads (ovaries or testes) or sexual anatomy say another. Parents of children with these kinds of conditions — known as intersex conditions, or differences or disorders of sex development (DSDs) — often face difficult decisions about whether to bring up their child as a boy or a girl. Some researchers now say that as many as 1 person in 100 has some form of DSD.
When genetics is taken into consideration, the boundary between the sexes becomes even blurrier. Scientists have identified many of the genes involved in the main forms of DSD, and have uncovered variations in these genes that have subtle effects on a person’s anatomical or physiological sex. What’s more, new technologies in DNA sequencing and cell biology are revealing that almost everyone is, to varying degrees, a patchwork of genetically distinct cells, some with a sex that might not match that of the rest of their body. Some studies even suggest that the sex of each cell drives its behaviour, through a complicated network of molecular interactions. “I think there’s much greater diversity within male or female, and there is certainly an area of overlap where some people can’t easily define themselves within the binary structure,” says John Achermann, who studies sex development and endocrinology at University College London’s Institute of Child Health.
These discoveries do not sit well in a world in which sex is still defined in binary terms. Few legal systems allow for any ambiguity in biological sex, and a person’s legal rights and social status can be heavily influenced by whether their birth certificate says male or female.
“The main problem with a strong dichotomy is that there are intermediate cases that push the limits and ask us to figure out exactly where the dividing line is between males and females,” says Arthur Arnold at the University of California, Los Angeles, who studies biological sex differences. “And that’s often a very difficult problem, because sex can be defined a number of ways.”
February 19, 2015
Published on 18 Feb 2015
Almost every cell in your body has the same DNA sequence. So how come a heart cell is different from a brain cell? Cells use their DNA code in different ways, depending on their jobs. Just like orchestras can perform one piece of music in many different ways. A cell’s combined set of changes in gene expression is called its epigenome. This week Nature publishes a slew of new data on the epigenomic landscape in lots of different cells. Learn how epigenomics works in this video.
February 12, 2015
Last month, Matt Ridley ran down the benefits to farmers, consumers, ecologists and the environment itself that the European Union has been resisting mightily all these years:
Scientifically, the argument over GM crops is as good as over. With nearly half a billion acres growing GM crops worldwide, the facts are in. Biotech crops are on average safer, cheaper and better for the environment than conventional crops. Their benefits accrue disproportionately to farmers in poor countries. The best evidence comes in the form of a “meta-analysis” — a study of studies — carried out by two scientists at Göttingen University, in Germany.
The strength of such an analysis is that it avoids cherry-picking and anecdotal evidence. It found that GM crops have reduced the quantity of pesticide used by farmers by an average of 37 per cent and increased crop yields by 22 per cent. The greatest gains in yield and profit were in the developing world.
If Europe had adopted these crops 15 years ago: rape farmers would be spraying far less pyrethroid or neo-nicotinoid insecticides to control flea beetles, so there would be far less risk to bees; potato farmers would not need to be spraying fungicides up to 15 times a year to control blight; and wheat farmers would not be facing stagnant yields and increasing pesticide resistance among aphids, meaning farmland bird numbers would be up.
Oh, and all that nonsense about GM crops giving control of seeds to big American companies? The patent on the first GM crops has just expired, so you can grow them from your own seed if you prefer and, anyway, conventionally bred varieties are also controlled for a period by those who produce them.
African farmers have been mostly denied genetically modified crops by the machinations of the churches and the greens, aided by the European Union’s demand that imports not be transgenically improved. Otherwise, African farmers would now be better able to combat drought, pests, vitamin deficiency and toxic contamination, while not having to buy so many sprays and risk their lives applying them.
I made this point recently to a charity that works with farmers in Africa and does not oppose GM crops but has so far not dared say so. Put your head above the parapet, I urged. We cannot do that, they replied, because we have to work with other, bigger green charities and they would punish us mercilessly if we broke ranks. Is the bullying really that bad? Yes, they replied.
Yet the Green Blob realises that it has made a mistake here. Not a financial mistake — it made a fortune out of donations during the heyday of stoking alarm about GM crops in the late 1990s — but the realisation that all it has achieved is to prolong the use of sprays and delay the retreat of hunger.
December 5, 2014
Michael White says we need to follow up our success in reading our own genetic code by decoding a different one:
There are thousands of mutations that occur in the breast cancer-linked genes BRCA1 and BRCA2. Some of these cause breast or ovarian cancer, while others are harmless. When we design a genetic test for predisposition to breast cancer, we have to know which ones to test for. The same is true of almost any gene that plays a role in disease — you’ll find many mutations in that gene in the general population, only some of which cause health problems. So how do we know which mutations to worry about?
We start by using the genetic code. The genetic code, cracked by scientists in the 1960s, makes it surprisingly easy to “read” our DNA and understand how a particular mutation affects a gene. As genetic testing takes on a bigger role in predicting, diagnosing, and treating disease, we rely on this code to help us make sense of the data. Unfortunately, the genetic code applies to less than two percent of our DNA. In an effort to read the rest, researchers are trying to crack a new genetic code — and this next one is turning out to be much more difficult to solve than the first. In fact, scientists may have to give up the idea that we can use a “code” to “read” the rest of our DNA.
When scientists were working out the original genetic code in the 1950s and ’60s, all sorts of complicated schemes were proposed to explain how information is stored in our genes. The problem they were trying to solve was how a gene, made of DNA, codes the information to make a particular protein — an enzyme, a pump, a piece of cellular scaffolding, or some other critical component of the cell’s working machinery. They were looking for a code that would translate the four-letter DNA alphabet of genes into the 20-letter amino acid alphabet of proteins.
Thanks to its simplicity, the genetic code is a powerful tool in our hunt for mutations that cause disease. Unfortunately, it has also led to the genetic equivalent of a drunk looking for his lost keys under the lamppost. Researchers have put much of their effort into looking for disease mutations in those parts of our genomes that we can read with the genetic code — that is, parts that consist of canonical genes that code for proteins. But these genes make up less than two percent of our DNA; much more of our genetic function is outside of genes in the relatively uncharted “non-coding” portions. We have no idea how many disease-causing mutations are in that non-coding portion — for some types of mutations, it could be as high as 90 percent.
October 17, 2014
…to oppose the notion of equality of opportunity these days is to be thought some kind of monstrous ultramontane reactionary, a Metternich or Nicholas I, who wants by means of repression to preserve the status quo in amber. Members of young audiences to which I have spoken have almost fainted with shock when I have said that I not only did not believe in equality of opportunity, but to the contrary found the very idea sinister in the extreme, and much worse than mere egalitarianism of outcome. To say to a young audience today that equality of opportunity is a thoroughly vicious idea is like shouting “God does not exist and Mohammed was not his prophet” at the top of one’s voice in Mecca.
Those who believe in equality of opportunity must want, if they take the idea seriously, to make the world not only just but fair. Genetic and family influences on the fate of people have to be eliminated, because they undoubtedly affect opportunities and make them unequal. Ugly people cannot be models; the deformed cannot be professional footballers; the retarded cannot be astrophysicists; the small of stature cannot be heavyweight boxers; I don’t think I have to prolong this list, as everyone can think of a thousand examples for himself.
Of course, it might be possible to level the field a little by legislating for equality of outcome: by, for example, insisting that ugly people are employed as models in proportion to their prevalence in the population. English novelist L.P. Hartley, author of The Go-Between, satirized such envious suppression of beauty (and, by implication, all egalitarianism other than that of equality under the law) in a novel called Facial Justice. It’s not a very good novel, as it happens, but the idea is very good; Hartley envisages a state in which everyone aspires to an “average” face, brought about by plastic surgery both for the abnormally ugly and the abnormally good-looking. Only in this way can the supposed injustice (actually it’s unfairness) of the genetic lottery be righted.
Hartley’s novel is a reductio ad absurdum of a pernicious idea. By contrast, Roosevelt’s “measurable quality of opportunity” is roughly achievable by human design: only roughly, of course, because some (though few) will still be excluded biologically, and there are (again few) upbringings so terrible that they preclude opportunity for the person to become anything much. But the aspiration to deny no one a “measurable quality of opportunity” is not intrinsically nasty, as is the insistence on equality of opportunity. On the contrary; our problem is, however, that the political arrangements needed to bring this about already exist in most Western countries, and still we are unhappy or discontented. Thus we — many of us, that is — attribute our unhappiness to inequality of opportunity for fear of looking elsewhere, including inward.
Theodore Dalrymple, “A More Sinister Equality”, Taki’s Magazine, 2014-04-06
May 7, 2014
In Forbes, Matthew Herper looks at how Novartis is transforming itself in an attempt to conquer cancer:
“I’ve been an oncologist for 20 years,” says Grupp, “and I have never, ever seen anything like this.” Emily has become the poster child for a radical new treatment that Novartis, the third-biggest drug company on the Forbes Global 2000, is making one of the top priorities in its $9.9 billion research and development budget.
“I’ve told the team that resources are not an issue. Speed is the issue,” says Novartis Chief Executive Joseph Jimenez, 54. “I want to hear what it takes to run this phase III trial and to get this to market. You’re talking about patients who are about to die. The pain of having to turn patients away is such that we are going as fast as we can and not letting resources get in the way.”
A successful trial would prove a milestone in the fight against the demon that has plagued living things since dinosaurs roamed the Earth. Coupled with the exploding capabilities of DNA-sequencing machines that can unlock the genetic code, recent drugs have delivered stunning results in lung cancer, melanoma and other deadly tumors, sometimes making them disappear entirely – albeit temporarily. Just last year the Food & Drug Administration approved nine targeted cancer drugs. It’s big business, too. According to data provider IMS Health, spending on oncology drugs was $91 billion last year, triple what it was in 2003.
But the developments at Penn point, tantalizingly, to something more, something that would rank among the great milestones in the history of mankind: a true cure. Of 25 children and 5 adults with Emily’s disease, ALL, 27 had a complete remission, in which cancer becomes undetectable. “It’s a stunning breakthrough,” says Sally Church, of drug development advisor Icarus Consultants. Says Crystal Mackall, who is developing similar treatments at the National Cancer Institute: “It really is a revolution. This is going to open the door for all sorts of cell-based and gene therapy for all kinds of disease because it’s going to demonstrate that it’s economically viable.”
H/T to Megan McArdle for the link.
January 13, 2014
Nathanael Johnson says he has taken more abuse over his articles on genetically modified organisms than anything else in his writing career. And he says he learned something from his research: that it actually doesn’t matter at all.
It’s a little awkward to admit this, after devoting so much time to this project, but I think Beth was right. The most astonishing thing about the vicious public brawl over GMOs is that the stakes are so low.
I know that to those embroiled in the controversy this will seem preposterous. Let me try to explain.
Let’s start off with a thought experiment: Imagine two alternate futures, one in which genetically modified food has been utterly banned, and another in which all resistance to genetic engineering has ceased. In other words, imagine what would happen if either side “won” the debate.
In the GMO-free future, farming still looks pretty much the same. Without insect-resistant crops, farmers spray more broad-spectrum insecticides, which do some collateral damage to surrounding food webs. Without herbicide-resistant crops, farmers spray less glyphosate, which slows the spread of glyphosate-resistant weeds and perhaps leads to healthier soil biota. Farmers also till their fields more often, which kills soil biota, and releases a lot more greenhouse gases. The banning of GMOs hasn’t led to a transformation of agriculture because GM seed was never a linchpin supporting the conventional food system: Farmers could always do fine without it. Eaters no longer worry about the small potential threat of GMO health hazards, but they are subject to new risks: GMOs were neither the first, nor have they been the last, agricultural innovation, and each of these technologies comes with its own potential hazards. Plant scientists will have increased their use of mutagenesis and epigenetic manipulation, perhaps. We no longer have biotech patents, but we still have traditional seed-breeding patents. Life goes on.
In the other alternate future, where the pro-GMO side wins, we see less insecticide, more herbicide, and less tillage. In this world, with regulations lifted, a surge of small business and garage-biotechnologists got to work on creative solutions for the problems of agriculture. Perhaps these tinkerers would come up with some fresh ideas to usher out the era of petroleum-dependent food. But the odds are low, I think, that any of their inventions would prove transformative. Genetic engineering is just one tool in the tinkerer’s belt. Newer tools are already available, and scientists continue to make breakthroughs with traditional breeding. So in this future, a few more genetically engineered plants and animals get their chance to compete. Some make the world a little better, while others cause unexpected problems. But the science has moved beyond basic genetic engineering, and most of the risks and benefits of progress are coming from other technologies. Life goes on.
The point is that even if you win, the payoff is relatively small in the broad scheme of things. Really, why do so many people care?
December 2, 2013
Kyle Smith on the FDA’s sudden interest in shutting down private DNA testing company 23andMe:
… the FDA has the power to regulate medical devices, which is the pretext it is using to stop 23andMe. Ordering it to stop selling its personal genome service, the FDA declared that the tube “is a device within the meaning of section 201(h) of the FD&C Act, 21 U.S.C. 321(h), because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment or prevention of disease, or is intended to affect the structure or function of the body.’
It would seem that 23andMe could simply put the words, “not intended for us in the diagnosis, cure, mitigation, treatment or prevention of disease” on its website and satisfy the FDA, but we all know that the motto of today’s federales is “We make it up as we go along.” The FDA seems determined to conduct a lengthy war with 23andMe.
Using the same reasoning, the FDA might as well shut down WebMd.com because people might type their symptoms into the site, and the response might affect whether or not they choose to go to a doctor. Any computer or iPhone thereby becomes a “medical device” that people can use for the “diagnosis, cure, mitigation, treatment or prevention of disease.”
Come to think of it, that thermometer you use to check your temperature is pretty dangerous too — it might give you either a false positive or a false negative — but why stop there? You exercise to mitigate or prevent disease, don’t you? Maybe the FDA should take your running shoes and your yoga pants away.
November 29, 2013
Nick Gillespie on the mindnumbingly awful exercise of FDA regulatory power in shutting down personal DNA testing company 23andMe:
Personal genetic tests are safe, innovative, and the future of medicine. So why is the most transparent administration ever shutting down a cheap and popular service? Because it can.
In its infinite wisdom, the Food and Drug Administration (FDA) has forbidden the personal genetic testing service 23andMe from soliciting new customers, claiming the company hasn’t proven the validity of its product.
The real reason? Because when it comes to learning about your own goddamn genes, the FDA doesn’t think you can handle the truth. That means the FDA is now officially worse than Oedipus’s parents, Dr. Zaius, and the god of Genesis combined, telling us that there are things that us mere mortals just shouldn’t be allowed to know.
23andMe allows you to get rudimentary information about your genetic makeup, including where your ancestors came from and DNA markers for over 240 different hereditary diseases and conditions (not all of them bad, by the way). Think of it as the H&M version of the haute couture genetic mark-up that Angelina Jolie had done prior to having the proactive mastectomy that she revealed this year.
Peter Huber of the Manhattan Institute, a conservative think tank, has an important new book out called The Cure in the Code: How 20th Century Law is Undermining 21st Century Medicine. Huber writes that whatever sense current drug-approval procedures once might have had, their day is done. Not only does the incredible amount of time and money — 12 years and $350 million at a minimum — slow down innovation, it’s based on the clearly wrong idea that all humans are the same and will respond the same way to the same drugs.
Given what we already know about small but hugely important variations in individual body chemistry, the FDA’s whole mental map needs to be redrawn. “The search for one-dimensional, very simple correlations — one drug, one clinical effect in all patients — is horrendously obsolete,” Huber told me in a recent interview. And the FDA’s latest action needs to be understood in that context — it’s just one more way in which a government which now not only says we must buy insurance but plans whose contours are dictated by bureaucrats who arbitrarily decide what is best for all of us.
October 6, 2013
Baylen Linnekin explains why compromise in the battle over genetically modified food ingredients is likely to be heartily supported by big business — because they can easily cover costs that their smaller competitors will not be able to afford:
Like it or not — and I’m in the not camp — a mandatory, uniform national GMO labeling scheme appears increasingly likely.
Major players on the business side, including Walmart, America’s leading grocer, and General Mills, which bills itself as “one of the world’s largest food companies,” have publicly tipped their hands that they’d support some sort of mandatory labeling.
As I noted this summer, Walmart held a meeting with FDA officials and others from the food industry earlier this year where, it was alleged, the grocer and other food sellers that have opposed state labeling requirements would push for the federal government to adopt a national GMO labeling standard.
And just last week, Ken Powell, the CEO of General Mills, announced at the company’s annual stockholders’ meeting that the company “strongly support[s] a national, federal labeling solution.”
Powell’s comments are a game changer.
But do they mean that anti-GMO activists and food companies are on the same page? Not by a longshot. Powell made clear in his remarks that the company supports “a national standard that would label foods that don’t have genetically engineered ingredients in them, rather than foods that do.” (emphasis mine)
I suspect that anti-GMO activists would hate that solution because it wouldn’t provide the “information” they want and because all of the significant testing and labeling costs of the mandatory scheme Powell suggests — along with any liability for not testing GMO-free foods or for mislabeling — would be borne by the GMO-free farmers and food producers they frequent (and by their customers, in the form of higher prices).
June 12, 2013
At Marginal Revolution, Alex Tabarrok links to a new paper by Peter Huber:
[. . .]
The current regime was built during a time of pervasive ignorance when the best we could do was throw a drug and a placebo against a randomized population and then count noses. Randomized controlled trials are critical, of course, but in a world of limited resources they fail when confronted by the curse of dimensionality. Patients are heterogeneous and so are diseases. Each patient is a unique, dynamic system and at the molecular level diseases are heterogeneous even when symptoms are not. In just the last few years we have expanded breast cancer into first four and now ten different types of cancer and the subdivision is likely to continue as knowledge expands. Match heterogeneous patients against heterogeneous diseases and the result is a high dimension system that cannot be well navigated with expensive, randomized controlled trials. As a result, the FDA ends up throwing out many drugs that could do good:
Given what we now know about the biochemical complexity and diversity of the environments in which drugs operate, the unresolved question at the end of many failed clinical trials is whether it was the drug that failed or the FDA-approved script. It’s all too easy for a bad script to make a good drug look awful. The disease, as clinically defined, is, in fact, a cluster of many distinct diseases: a coalition of nine biochemical minorities, each with a slightly different form of the disease, vetoes the drug that would help the tenth. Or a biochemical majority vetoes the drug that would help a minority. Or the good drug or cocktail fails because the disease’s biochemistry changes quickly but at different rates in different patients, and to remain effective, treatments have to be changed in tandem; but the clinical trial is set to continue for some fixed period that doesn’t align with the dynamics of the disease in enough patients
Or side effects in a biochemical minority veto a drug or cocktail that works well for the majority. Some cocktail cures that we need may well be composed of drugs that can’t deliver any useful clinical effects until combined in complex ways. Getting that kind of medicine through today’s FDA would be, for all practical purposes, impossible.
The alternative to the FDA process is large collections of data on patient biomarkers, diseases and symptoms all evaluated on the fly by Bayesian engines that improve over time as more data is gathered. The problem is that the FDA is still locked in an old mindset when it refuses to permit any drugs that are not “safe and effective” despite the fact that these terms can only be defined for a large population by doing violence to heterogeneity. Safe and effective, moreover, makes sense only when physicians are assumed to be following simple, A to B, drug to disease, prescribing rules and not when they are targeting treatments based on deep, contextual knowledge that is continually evolving