Rapid genetic degradation refutes evolutionary fairytales

There are 3 billion base pairs in the human genome, and a mistake or mutation in just one single letter can have a significant impact on a person's health

https://www.latimes.com/science/sciencenow/la-sci-sn-dna-gene-editing-20171025-story.html

Excerpt: "In the new study, published Wednesday in the journal Nature, the authors present a second base editor that can convert the base adenine (A) into the base inosine (I), which acts like guanine (G).

The new work is significant because it will allow scientists to use base editing to address many more single-letter mutations than was previously possible, said Krishanu Saha, a biomedical engineer at the University of Wisconsin Madison who was not involved with the research.

"This is another nice example of using protein engineering to diversify the types of edits that the CRISPR system can accomplish," he said.
 

There are 3 billion base pairs in the human genome, and a mistake or mutation in just one single letter can have a significant impact on a person's health.

Of more than 50,000 genetic changes currently known to be associated with disease in humans, 32,000 of those are caused by the simple swap of one base pair for another, Liu said.

The group's first base editing tool, which had the effect of converting a C to a T, has the potential to correct 14% of human diseases associated with a single-letter mutation. The new tool will allow researchers to address an additional 48% of these types of diseases.
The type of mistake that can be targeted by the new base editor is "by far, the most common kind" in people "and probably all living systems," Liu said."

My comment: Here's a brief summary of facts regarding genetic entropy:

- There are 628,685 gene-disease associations in human genome worldwide (DisGeNet, Jan 2019)

- One in five 'healthy' adults may carry disease-related genetic mutations

- Every time human DNA is passed from one generation to the next it accumulates 100–200 new mutations, according to a DNA-sequencing analysis of the Y chromosome.

- Exome Aggregation Consortium (ExAC) released a report after analyzing the genome of over 60,000 individuals. 1,2 billion genes were analyzed and not a single beneficial mutation was found.

- The list of human genetic diseases is very long.

- Modern science is not aware of random, fully beneficial DNA mutations.

- Honest scientists realize that human genetic degradation is an inevitable phenomenon

- Rapid genetic degradation is occurring everywhere in the wild.

Epigenetic memory upends a basic tenet of biology, the Second Law of Biology

Nerve cells can transmit messages to future generations not via the DNA, but by epigenetic changes

https://www.haaretz.com/science-and-health/worms-help-israeli-scientists-rewrite-basics-of-genetics-1.7345758

For biologists, the discovery is shocking. “These findings go against one of the most basic dogmas in modern biology,” Rechavi says. “It was long thought that brain activity could have absolutely no impact on the fate of the progeny.” Evidently the nematode didn’t hear of the Second Law of Biology.

Excerpts: "Nematodes have just upended the Second Law of Biology, researchers at Tel Aviv University reported Thursday in the journal Cell. Using worms, Prof. Oded Rechavi, with Rachel Posner and Itai Toker, have proved for the first time that true epigenetic inheritance does exist.

A worm’s reaction to the environment can pass from generation to generation without change in the DNA itself. The team also discovered exactly how this nongenetic legacy is achieved.

“The nervous system is unique in its ability to integrate responses about the environment as well as bodily responses. The idea that it could also control the fate of an organism’s progeny is stunning.”

The Second Law of Biology, aka the Weismann barrier, states that inherited information in the germline (sperm and egg cells) shalt be isolated from environmental influences.But in the simple nematode C. elegans, progress was made in recent years. Mechanisms were identified that act in parallel with the DNA.

In this new study, Rechavi and colleagues show that the worm’s ability to seek food can be governed by inheritance from the ancestor’s neurons, causing epigenetic silencing of a specific gene in the progeny.
This gene was shown to control the decision of whether to forage (go look for food, leave your safe place) or whether to stay put and avoid the risk.
 

If the worm can’t make the epigenetic control mechanism, the gene over-expresses and the worm can’t seek food.

And what is the mechanism controlling the gene? It turns out to be a type of small RNA molecule made in the worm nerve cells.

A worm that can’t make the small RNAs can’t seek food.

But if that worm’s mother or even their grandmother could make the small RNA in the nervous system — then the worm can seek food.

The worm inherited the small RNAs from Mama, not via the DNA. Ergo, somehow Mama’s nerve cell conveyed the change to Mama’s germ cells.

The epigenetic effect can persist three to five generations in nature, even hundreds of generations if the worms are genetically altered, Rechavi says.

Their discovery upends a basic tenet of biology, the Second Law: Inherited information in the germline is supposed to be isolated from what happens in somatic cells (the cells of the body, not the germ cells) and from environmental influences.

In the lab, nematodes that couldn’t make the small RNAs exhibited defective food identification skills. When the researchers restored the ability to produce small RNAs in neurons, the nematodes moved toward food efficiently once again. This effect was maintained for multiple generations even though the progeny did not have the ability to produce small RNAs themselves.

For biologists, the discovery is shocking. “These findings go against one of the most basic dogmas in modern biology,” Rechavi says. “It was long thought that brain activity could have absolutely no impact on the fate of the progeny.” Evidently the nematode didn’t hear of the Second Law of Biology.

Link to the original study.

My comment: Epigenetic memory makes it possible for an organism to transfer valuable information from parents to offspring. The mechanism is very complex and points to design. Scientists are still wondering if this mechanism is present in mammalian cells. Of course it is. There are thousands of different short and long noncoding RNA molecules in human sperm, for example. Their job is to transfer epigenetic memory to children. This information is stored in histone epigenetic markers. Most of human traits and characteristics are inherited in this way. But gene-centric theory of evolution resists findings like this. That's why it's pseudoscience. Don't get lost my friends.

Impossibility of abiogenesis

Unwillingness to acknowledge the impossibility of abiogenesis has led to sixty plus years of failure in the field

https://osf.io/p5nw3/?fbclid=IwAR2X2n6gXCEhqACzWCzbOctKHsFeE7N_5yuCefQDN3V7SckTepG-Py4WJgw

Summary:

• Natural variation in environmental variables, particularly stream flow variation, works against natural processes providing a required steady flow of products.
• Randomness appears to prevent formation of usable building block amino acids and nucleotides.
• Randomness prevents formation of usable polymers of protein or nucleic acid.
• An autonomous, living cell needs all of its components to function properly, it cannot be divided beyond certain basic systems.
• Over the past sixty years, there have been reputedly thousands of experiments performed representing various postulated steps. None have been able to provide product usable as feedstock for its successor, which is the standard defining success within this analysis.  
  
• Virchow’s aphorism and emergence work together to require the first cell to appear fully assembled from the beginning.
• Since information is an abstract entity, as is also the code mapping it to a medium, there are no physical laws capable of creating it.
• Nature itself provides conclusive evidence that natural processes are incapable of assembling a living cell. Wherever one looks there are problems.
• There is a large body of evidence—essentially all experiments in abiogenesis performed since its inception sixty plus years ago—that appear to be consistent with the hypothesis presented in this paper. Randomization prevails.
  

My comment: Evolution believers have serious problems. Over the past sixty years, every attempt to prove abiogenesis possible have failed. Experiments and observations don't support the theory of abiogenesis or evolution. Don't get lost my friends.

p.s. Thanks to Otangelo Grasso for addressing this study to us. Even it's a preprint, it offers valuable information and helps us understand why abiogenesis is impossible.

Rapid mtDNA mutation rate refutes evolutionary timescales

Phylogenetic studies have substantially underestimated the rate of mtDNA divergence

http://www.dnai.org/teacherguide/pdf/reference_romanovs.pdf

Excerpts: "Evolutionists have assumed that the clock is constant, ticking off mutations every 6000 to 12,000 years or so. But if the clock ticks faster or at different rates at different times, some of the spectacular results--such as dating our ancestors' first journeys into Europe at about 40,000 years ago--may be in question. "We've been treating this like a stopwatch, and I'm concerned that it's as precise as a sun dial," says Neil Howell, a geneticist at the University of Texas Medical Branch in Galveston. "I don't mean to be inflammatory, but I'm concerned that we're pushing this system more than we should."

"The researchers sequenced 610 base pairs of the mtDNA control region in 357 individuals from 134 different families, representing 327 generational events, or times that mothers passed on mtDNA to their offspring. Evolutionary studies led them to expect about one mutation in 600 generations (one every 12,000 years). So they were "stunned" to find 10 base-pair changes, which gave them a rate of one mutation every 40 generations, or one every 800 years. The data were published last year in Nature Genetics, and the rate has held up as the number of families has doubled, Parsons told scientists who gathered at a recent international workshop* on the problem of mtDNA mutation rates."

 

"Regardless of the cause, evolutionists are most concerned about the effect of a faster mutation rate. For example, researchers have calculated that "mitochondrial Eve"--the woman whose mtDNA was ancestral to that in all living people--lived 100,000 to 200,000 years ago in Africa. Using the new clock, she would be a mere 6000 years old."

My comment: True scientific observations about mtDNA mutation rate using close maternal relatives reveal that the mtDNA mutation rate is much higher than phylogenetic studies suggest:

https://www.ncbi.nlm.nih.gov/pubmed/9090380

Excerpt: "We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck."

My comment: When using true scientific methods and when observations are made by using concrete samples and data, then everything points to recent creation. What might the implications of observed rapid mtDNA mutations be for studies like this, in which traditional, slow mtDNA mutation rate was used? Suddenly, everything points to Biblical creation.

99.9% of frames are missing

The theory of evolution has no scientific basis

The fossil record is like a film of evolution from which 999 of every 1,000 frames have been lost on the cutting room floor.
(National Geographic November, 2004 p.25)

Evolution believers have seen only 0.1% of frames and based on that, they have made an imaginary film by which they maintain their fallacious theory. 99.9% of the film is based on their imagination.

Darwin himself was well aware of the problems that the fossil record posed for his theory:

Why then is not every geological formation and every stratum full of such intermediate links? Geology assuredly does not reveal any such finely graduated organic chain; and this, perhaps, is the most obvious and gravest objection which can be urged against my theory. The explanation lies, as I believe, in the extreme imperfection of the geological record.Charles Darwin (1859), The Origin of Species, p. 280.

These are very serious problems for the theory of evolution. This is why it's not science. The theory of evolution is wishful thinking, guesses, utopia, lies and deception. There should be millions and millions of transitionals if the theory of evolution were true. But today, evolution believers have only a few candidates.

Modern scientists have realized that species are islands in sequence space. Intermediates disappear. Everything is just like the Bible says. Don't get lost my friends.

If evolution were true...

If evolution were true...

If evolution were true, there would be millions of evidence for it because there are millions of species on Earth.

In reality, species belong to kinds (genus) that seem to have an insurmountable chasm. Cats remain as cat kinds, bacteria as bacteria, dogs as Canid genus, etc. This confirms the announcement of the Bible. Organisms adapt and vary according to the principle of 'After its kind'. Dogs, cats and bacteria experience variation. Apes experience variation. But humans don't experience variation. According to the Bible, human was created in the image of God, but not by the principle of 'After his kind'. Thus, the Bible is also very accurate here.

If evolution were true, we could observe new structures and functions in organisms.

In reality, however, this has never been observed to happen. The few times that new structures are believed to have appeared have been due to regulation of existing biological information, that is, epigenetic switches. A good example of this is the Cecal valve in Italian wall lizard, for benefiting digestion in the use of plant-based food. Rapid eye loss and restoration of cave fish are also good examples of epigenetic switching.

If evolution were true, development would be a continuous process that would be noticeable as a clear change in a positive direction, along with increase in amount of biological information.

Ribosome of E. Coli. It's made up of several complex proteins 

and RNAs. Production of proteins is not possible without this 

complex molecular machine. Chicken-egg dilemma.

In reality, adaptation of organisms is based on regulation of existing complex information and alternative epigenetic programs. However, variation of these programs results in information corruption and genetic degradation. This phenomenon can be observed throughout nature as well as in human genome. Corruption of information leads to defective DNA sequences that the cell stores at the ends of chromosomes as telomeres. Chromosomes combine and their total number decreases. There is thousands of scientific evidence for this. There are 628,685 gene-disease associations in human genome worldwide but the number of fully beneficial mutations is zero.
 

If evolution were true, we would not need to have this debate, because there would be so much scientific and convincing evidence that nobody would have to doubt whether or not evolution is happening.

In reality, evolution theory is maintained by atheistic forces that do not allow criticism of evolutionary theory. Atheists will belittle, exert pressure, profile, bully, troll, and threaten those who dare to present appropriate criticism of evolutionary theory. And that is the best indication that the evolutionary theory is a belief system. The evolutionary theory has nothing to do with observed and serious science. When an evolution believer is asked to provide evidence for evolution, the answer is that human and fish have a few similar DNA sequences and that sickle cell anemia is a beneficial mutation. In reality, evolution believers are not able to show that a kind (genus) could change to another kind . They claim that genetic degradation is also part of evolution, but this is a dishonest escape. If we can't observe anything else but regulation of existing biological information and corruption of information, it is clear that evolution never happened. Don't get lost my friends.

Translation of mRNA more complex than expected

Genetic code in mRNA seems to be very complex, energy efficient and optimally organized

https://phys.org/news/2019-06-genes-complex.html?fbclid=IwAR3M4udmXjH6WYY5JwVPAjoYrS-sraYdIQ7oH0cGOfVOzlFIcdzrnFBld5Y

Excerpt: "The genetic code is translated in groups of 3 letters, each resembling a word, which is translated into a single part of the protein. If a ribosome starts translating the code at the wrong position, a shift in the 3-letter-code can occur. For example, the sentence below should read:

"the man saw his new red car"

However, if a ribosome starts translating this sentence one letter too late, the sentence would read:

"hem ans awh isn ewr edc ar"

In the case of the genetic code, this phenomenon is called 'out-of-frame' translation. Sanne Boersma, researcher at the Hubrecht Institute explains: "As illustrated by the example sentence, out-of-frame translation has a big effect on the protein and usually results in a protein that behaves differently and can damage the cell." Until now, it was unclear how the ribosome knows where to start translating the code, and how often the ribosome gets it wrong.

 

A big surprise

The researchers discovered that out-of-frame translation happens surprisingly frequently. In extreme cases, almost half of all the proteins that were built, used a different reading frame or code than the expected code. These surprising findings show that the genetic information stored in our DNA is far more complex than previously thought. Based on the new study, our DNA likely encodes thousands of previously unknown proteins with unknown functions. Sanne Boersma: "Because of our study, we can now ask very important questions: what do all these new proteins do? Do they have important functions in our body or are they waste side-products of translation that can damage our cells?" "

My comment: Scientists have thought that genetic code in mRNA is limited to certain short sequences, so called codons. These newest discoveries point out that this is not the case. Every codon can be a start codon. What the article didn't emphasize, is the cell's ability to produce a huge variety of different RNA molecules by transcribing just one DNA strand. The genetic code is poly-functional, overlapping, embedded and multi-layered information. It's so optimally organized that it's clearly designed by God. Don't get lost my friends.

Loss of genetic diversity is an inevitable phenomenon in nature

Small populations tend to lose genetic diversity more quickly than large populations

https://www.purdue.edu/captivebreeding/effect-of-small-population-size/

Excerpt: "Population size, technically the effective population size, is related to the strength of drift and the likelihood of inbreeding in the population. Small populations tend to lose genetic diversity more quickly than large populations due to stochastic sampling error (i.e., genetic drift). This is because some versions of a gene can be lost due to random chance, and this is more likely to occur when populations are small. Additionally, smaller population size means that individuals are more likely to breed with close relatives. In closed populations, individuals will be more closely related to each other compared to individuals in the previous generation. For example, in a hypothetical population consisting of only four individuals, if two pairs each produced two offspring (meaning that four new individuals are present in the next generation), the offspring must either mate with a sibling, a parent, or an individual from the other pair. Assuming they choose the non-sibling/non-parent option, all of the offspring in the third generation must mate with individuals that have the same grandparents or choose to forgo reproduction. Although this example is extreme due to the very small hypothetical population, the same patterns and forces are present in larger – albeit still small – populations.
 

Although the mechanism of the loss of genetic diversity due to inbreeding and drift is different, the effects on populations are the same. Both inbreeding and drift reduce genetic diversity, which has been associated with an increased risk of population extinction, reduced population growth rate, reduced potential for response to environmental change, and decreased disease resistance, which impacts the ability of released individuals to survive and reproduce in the wild."

My comment: Here's a couple of examples of rapid loss of genetic diversity:

Cats are going extinct: 12 most endangered feline species.
Genetic meltdown just in five generations.
Common denominator for endangered species - loss of genetic diversity

Small populations tend to lose genetic diversity more quickly than large populations, but in every scenario, genetic diversity is lost, faster or slower.

From where could populations gain new genetic information? Nowhere. Only pre-existing information from inside the population.

Evolution never happened. The Bible tells us the truth. 

Denis Noble, one of the leading evolution scientists: "Gene-Centric Neo-Darwinism has failed."

The gene-centric view resists new findings and deprecates epigenetic mechanisms

https://thebestschools.org/dialogues/evolution-denis-noble-major-statement/

Summary:

1. Major diseases still plague humanity.

The gene-centric view has failed in one of its major claims, i.e., that it would result, through sequencing genes, in curing the major diseases that plague humanity.

2. Privileging any one level in biological systems cannot be justified.

3. The gene-centric view has damaging consequences.

The gene-centric view has had profoundly damaging (even if not intended) consequences in sociology, economics, politics, and many other areas of the humanities and social sciences.

4. The gene-centric view resists new findings.

The gene-centric view has had to gyrate in a contorted way to accommodate one new finding after another. The final straw for me was a supporter of neo-Darwinism purporting to accept the inheritance of acquired characteristics. This is like eating your own tail.

5. The gene-centric view claims parsimony.

6. The gene-centric view claims to settle the question of Lamarckism.

Part of the reason lies in the way in which Crick's Central Dogma was greeted by neo-Darwinists as welcome and impressive support for the Weismann Barrier idea. The two reinforced each other. The isolation of the germ-line seemed to be confirmed spectacularly by the finding that DNA codes for proteins through the intermediate of RNA, whereas protein sequences do not code for DNA or RNA. This is represented by the shaded downward-pointing arrows below.

 The actual situation is much more complex and has been widely misunderstood.

I wonder what Descartes would think of the modern experiments on cross-species clones. If Descartes, Weismann, and Crick were right, then transferring the nucleus of one species into the fertilized egg cell of another species to replace its removed nucleus should unambiguously lead to an organism that matches the blueprint of the nucleus. So, what do we find? First, they would be shocked to find that for most cross-species clones, the experiment doesn't even work. Usually, the embryonic development freezes at some point. There is therefore an incompatibility between the genetic material of the donor nucleus and the recipient egg cell. Second, in the rare cases where the experiment works, we obtain an organism intermediate between the two species.

The most spectacular example of this kind of experiment comes from work done at the Wuhan Fish Institute in China by Yonghua Sun and his colleagues in 2005 using two different species of fish, where the nucleus of one species was used to replace the nucleus in a fertilized egg cell of the other species. The outcome in the anatomy of the adult that resulted from this cross was determined by the cytoplasmic structures and expression patterns of the egg cells, as well as the transferred DNA. The basic features of structural organization both of cells and of multicellular organisms must have been determined by physical constraints before the relevant genomic information was developed.

7. The gene-centric view claims that epigenetic inheritance is short-lived.

8. The gene-centric view claims genetic change is always random with respect to function.

9. The gene-centric view claims neo-Darwinism is obvious and necessarily true.

10. The gene-centric view appeals to authority.

Even 'designed' mutations are harmful - poly-functional genome should not be edited

CRISPR Babies Could Be at Risk of Early Death - This is a lesson in humility

Link to the article

Excerpt: "About half a year after Chinese scientist He Jiankui first brought gene-edited babies into the world, cooler heads have finally prevailed: scientists pored over hundreds of thousands of medical records to learn how the genes that He altered affect human health.

He's team gene-edited the twin babies - and a third baby due this summer - to knock out a gene called CCR5 in hopes that it would render them immune to HIV.

But according to new research published in the journal Nature Medicine, people with that genome are 21 percent more likely to die before reaching the average life expectancy.

Scientists from UC Berkeley searched a repository of human subjects' DNA to look for the same variants of the CCR5 that He Jiankui gave the children, NPR reports.

They found that the same genome that might grant greater immunity from HIV also makes people vulnerable to dangerous flus and West Nile virus.

"What we found is that they had significantly increased mortality," lead researcher Rasmus Nielsen told NPR. "It's rather substantial. We were quite surprised the effect was this large."
 

He's experiments have spurred many scientists to recommend against gene-hacking human embryos until we know more.

"This is a lesson in humility," George Daley, dean of Harvard Medical School, told NPR.

"Even when we think we know something about a gene, we can always be surprised and even startled, like in this case, to find out that a gene we thought was protective may actually be a problem."

My comment: Multiple overlapping and poly-functional DNA shouldn't be edited. DNA is passive information resource but it is layered and packaged in a very optimal way. For example, there are only ~19,000 DNA strands used for protein encoding in human genome but the number of different protein isoforms in a human body is up to several millions. Our cells are capable of producing thousands of different proteins by reading and using just one DNA strand. Modification is done at RNA level.

If designed mutations only mess up the system, how come could random errors result in evolution?

Decades of early research on the genetics of depression were built on nonexistent foundations. How did that happen?

Well, if scientists are publishing crap, why should we believe global warming and evolution?

https://www.theatlantic.com/science/archive/2019/05/waste-1000-studies/589684/

Excerpt: "In 1996, a group of European researchers found that a certain gene, called SLC6A4, might influence a person’s risk of depression.

It was a blockbuster discovery at the time. The team found that a less active version of the gene was more common among 454 people who had mood disorders than in 570 who did not. In theory, anyone who had this particular gene variant could be at higher risk for depression, and that finding, they said, might help in diagnosing such disorders, assessing suicidal behavior, or even predicting a person’s response to antidepressants.

Back then, tools for sequencing DNA weren’t as cheap or powerful as they are today. When researchers wanted to work out which genes might affect a disease or trait, they made educated guesses, and picked likely “candidate genes.” For depression, SLC6A4 seemed like a great candidate: It’s responsible for getting a chemical called serotonin into brain cells, and serotonin had already been linked to mood and depression. Over two decades, this one gene inspired at least 450 research papers.

But a new study—the biggest and most comprehensive of its kind yet—shows that this seemingly sturdy mountain of research is actually a house of cards, built on nonexistent foundations.

Richard Border of the University of Colorado at Boulder and his colleagues picked the 18 candidate genes that have been most commonly linked to depression—SLC6A4 chief among them. Using data from large groups of volunteers, ranging from 62,000 to 443,000 people, the team checked whether any versions of these genes were more common among people with depression. “We didn’t find a smidge of evidence,” says Matthew Keller, who led the project.

Between them, these 18 genes have been the subject of more than 1,000 research papers, on depression alone. And for what? If the new study is right, these genes have nothing to do with depression. “This should be a real cautionary tale,” Keller adds. “How on Earth could we have spent 20 years and hundreds of millions of dollars studying pure noise?”
 

“What bothers me isn’t just that people said [the gene] mattered and it didn’t,” wrote the pseudonymous blogger Scott Alexander in a widely shared post. “It’s that we built whole imaginary edifices on top of this idea of [it] mattering.” Researchers studied how SLC6A4 affects emotion centers in the brain, how its influence varies in different countries and demographics, and how it interacts with other genes. It’s as if they’d been “describing the life cycle of unicorns, what unicorns eat, all the different subspecies of unicorn, which cuts of unicorn meat are tastiest, and a blow-by-blow account of a wrestling match between unicorns and Bigfoot,” Alexander wrote.

Border and Keller’s study may be “bigger and better” than its predecessors, but “the results are not a surprise,” says Cathryn Lewis, a geneticist at Kings College London. Warnings about the SLC6A4/depression link have been sounded for years. When geneticists finally gained the power to cost-efficiently analyze entire genomes, they realized that most disorders and diseases are influenced by thousands of genes, each of which has a tiny effect. To reliably detect these minuscule effects, you need to compare hundreds of thousands of volunteers. By contrast, the candidate-gene studies of the 2000s looked at an average of 345 people! They couldn’t possibly have found effects as large as they did, using samples as small as they had. Those results must have been flukes—mirages produced by a lack of statistical power. That’s true for candidate-gene studies in many diseases, but Lewis says that other researchers “have moved on faster than we have in depression.”

Marcus Munafò of the University of Bristol remembers being impressed by the early SLC6A4 research. “It all seemed to fit together,” he says, “but when I started doing my own studies in this area, I began to realize how fragile the evidence was.” Sometimes the gene was linked to depression; sometimes it wasn’t. And crucially, the better the methods, the less likely he was to see such a link. When he and others finally did a large study in 2005—with 100,000 people rather than the 1,000 from the original 1996 paper—they got nothing.

“You would have thought that would have dampened enthusiasm for that particular candidate gene, but not at all,” he says. “Any evidence that the results might not be reliable was simply not what many people wanted to hear.” In fact, the pace at which SLC6A4/depression papers were published accelerated after 2005, and the total number of such papers quadrupled over the next decade. “We’re told that science self-corrects, but what the candidate-gene literature demonstrates is that it often self-corrects very slowly, and very wastefully, even when the writing has been on the wall for a very long time,” Munafò adds.

Many fields of science, from psychology to cancer biology, have been dealing with similar problems: Entire lines of research may be based on faulty results. The reasons for this so-called reproducibility crisis are manifold. Sometimes, researchers futz with their data until they get something interesting, or retrofit their questions to match their answers. Other times, they selectively publish positive results while sweeping negative ones under the rug, creating a false impression of building evidence.

Beyond a few cases of outright misconduct, these practices are rarely done to deceive. They’re an almost inevitable product of an academic world that rewards scientists, above all else, for publishing papers in high-profile journals—journals that prefer flashy studies that make new discoveries over duller ones that check existing work. People are rewarded for being productive rather than being right, for building ever upward instead of checking the foundations. These incentives allow weak studies to be published. And once enough have amassed, they create a collective perception of strength that can be hard to pierce.

Terrie Moffitt of Duke University, who did early influential work on SLC6A4, notes that the candidate-gene approach has already been superseded by other methods. “The relative volume of candidate-gene studies is going way down, and is highly likely to be trivial indeed,” she says. Border and Keller disagree. Yes, they say, their geneticist colleagues have largely abandoned the approach, which is often seen as something of a historical embarrassment. “But we have colleagues in other sciences who had no idea that there was even any question about these genes, and are doing this research to this day,” Border says. “There’s not good communication between subfields.” (A few studies on SLC6A4 and depression have even emerged since their study was published in March.)


The goalposts can also change. In one particularly influential study from 2003, Avshalom Caspi, Moffitt, and others claimed that people with certain versions of SLC6A4 were more likely to become depressed after experiencing stressful life events. Their paper, which has been cited more than 8,000 times, suggested that these genes have subtler influences, which only manifest in certain environments. And if bigger studies found that the genes had noinfluence, it’s probably because they weren’t accounting for the experiences of their volunteers.

Border and Keller have heard that argument before. So, in their study, they measured depression in many ways—diagnosis, severity, symptom count, episode count—and they accounted for environmental factors such as childhood trauma, adulthood trauma, and socioeconomic adversity. It didn’t matter. No candidate gene influenced depression risk in any environment.

But Suzanne Vrshek-Schallhorn of the University of North Carolina at Greensboro says that Border’s team didn’t assess life experiences with enough precision. “I cannot emphasize enough how insufficient the measures of the environment used in this investigation were,” she says. “Even for measures that fall below gold-standard stress-assessment approaches, they represent a new low.” By using overly simple yes-or-no questionnaires rather than more thorough interviews, the team may have completely obscured any relationships between genes and environments, Vrshek-Schallhorn claims. “We should not get starry-eyed about large sample sizes, when measure validity is compromised to achieve them. We need to emphasize both quality and quantity.”

But Border argues that even if there had been “catastrophic measurement error,” his results would stand. In simulations, even when he replaced half the depression diagnoses and half the records of personal trauma with coin flips, the study would have been large enough to detect the kinds of effects seen in the early candidate-gene papers.

Similar debates have played out in other fields. When one group of psychologists started trying to reproduce classic results in much larger studies, their peers argued that any failures might simply be due to differences between the new groups of volunteers and the originals. This excuse has eroded with time, but to Border, it feels familiar. “There’s an unwillingness to part with a previous hypothesis,” he says. “It’s hard to wrap your head around the fact that maybe you were on a wild goose chase for years.”

Keller worries that these problems will be used as ammunition to distrust science as a whole. “People ask, Well, if scientists are publishing crap, why should we believe global warming and evolution?” he says. “But there’s a real difference: Some people were skeptical about candidate genes even back in the 1990s. There was never unanimity or consensus in the way there is for human-made global warming and the theory of evolution.”

Nor, he says, should his work be taken to mean that genes don’t affect depression. They do, and with newer, bigger studies, researchers are finally working out which ones do. If anything, the sordid history of the candidate-gene approach propelled the development of better methods. “I feel like the field of psychiatric genetics felt really burned coming out of the candidate-gene era, and took strides to make sure it won’t happen again.” That includes sharing data openly, and setting standards for how large and powerful studies need to be.

Dorothy Bishop of the University of Oxford argues that institutions and fundersthat supported candidate-gene work in depression should also be asking themselves some hard questions. “They need to recognize that even those who think they are elite are not immune to poor reproducibility, which leads to a huge amount of waste,” she says.

“We have got to set up a system, or develop a culture, that rewards people for actually trying to do it right,” adds Keller. “Those who don’t learn from the past are doomed to repeat it.” "

My comment: DNA doesn't determine organismal characteristics. DNA genes are not drivers, they are followers. DNA molecule is just passive information resource.

Btw, did you know that only ~20% of research made in fields of biology is reliable according to latest studies? Science is suffering from serious replication crisis.

https://ipfs.io/ipfs/QmXoypizjW3WknFiJnKLwHCnL72vedxjQkDDP1mXWo6uco/wiki/Replication_crisis.html