CRISP(R)- Y GENETICS.

CRISPR Cas9: Editing genes, Solving mysteries. 

In the amazing and surprisingly accurate, Sci-film Gattaca, a geneticist explains to two parents that an embryo that he has programmed to never have any ‘prejudicial conditions, such as alcoholism and obesity is ‘simply the best of you. [They] could conceive naturally a thousand times and never get such a result’. Whilst the idea of creating a child to be exactly what you would want them to be is a concept that appears to belong to Marvel movies, the potential of CRISPR Cas9 can make the future depicted in Gattaca a reality.

CRISPR Cas-9 describes a natural system found in bacteria, that has been utilized for genetic engineering and may be the future of genetics and genomics. In 2020, Jennifer Doudna and Emmanuelle Charpentier, were awarded the Nobel Prize in Chemistry for their work in developing CRISPR.

                                                                  Jennifer Doudna and Emmanuelle Charpentier.

The winners of the 2020 Nobel Prize in Chemistry- for their work in developing CRISPR. Multiple other scientists have contributed to CRISPR including, but not limited to: Francisco Mojica, Gilles Vergnaud and Christine Pourcel, Alexander Bolotin, Luciano Marraffini and Erik Sontheimer, and Sylvain Moineau

                                

In 2025, CPRISR is still making waves. In May this year, CRISPR was first used as a personalised therapy for an infant born with a metabolic disorder. Casgevy, the first CRISPR-based gene therapy has now been approved for use in treating sickle cell disorder and beta thalassemia, has been approved and is now treating patients across 50 sites worldwide. 

But it appears that CRISPR is not only for the future; it is also for solving the past. Despite the multiple experiments conducted and discoveries made, the genome is still full of many mysteries that have never been solved.

In September 2021, Daniel M.Sapozhnikov and Moshe Szyf made their own contribution to the work done to understand the genome by using CRISPR Cas9. After four decades of research, the relationship between DNA methylation and gene expression is still unknown. DNA methylation is known to be associated with transcriptional regulation  and has been for almost half a century- but  it was unclear whether DNA methylation is the force behind the transcriptional change or whether it is the transcriptional change that causes the methylation.

The beginner’s guide to DNA methylation.

DNA methylation is a form of epigenetics; these are changes in activity or the function of the genes. It is common misconception that every gene that the DNA codes for is constantly active and constantly producing protein. Actually, a gene can be active or non-active, based on what proteins are actually required. Lung cells may need different proteins than muscle cells for example. DNA methylation is used to turn genes 'On' or 'Off'.  When a methyl group - a carbon with three hydrogens is added to the DNA sequence, the gene is turned off.  It is important to remember that the DNA sequence itself does not change. I always think of it like adding charms to a charm bracelet. The unwound DNA resembles a chain -this does not change, but charms- the methyl groups are added.

                                                                                How DNA Methylation works.

A methyl group consist of a carbon bonded to three hydrogens. Carbon molecules must always have four bonds so bind to a cytosine. The methyl groups will cause silencing of the gene- meaning that when the DNA goes though transcription, this region of DNA will not be expressed. DNA methylation is catalysed by DNA methyltransferases (Dnmts). Dnmt3a and Dnmt3b are known are de novo Dnmt, due to their ability to add methylation to unmodified DNA (Moore et al, 2012). Basically, in the charm bracelet analogy, these are the two ‘hands’  that add the charms to a brand new chain.

Now imagine that in the charm bracelet, charms can only be added to certain links. These certain links start off as 4 links apart but then become close and closer, giving regions where there are several charms hanging of the chains but other regions where there are barely any. These regions are the CpG islands -or CGI.

In mammalian genomes, regions of high guanine and cytosine content contain a high amount of CpG nucleotides. The methyl groups would only be binding to a cytosine located next to a guanine. In between them will be a phosphate molecule.

These islands tend to be located in gene promotor and enhancer regions.  These are areas of DNA that control whether a gene can produce a protein in a process called transcription. But they can also be found within genes themselves. Typically, they are maintained in an unmethylated state and play a role in control of gene expression.

What was unknown was whether the DNA methylation was actually CAUSING the transcriptional change or the DNA methylation was just indicating that a transcriptional change was occurring

In other words, in a variation of the old chicken and the egg debate- what came first- DNA methylation or the transcriptional change- the turning on or off of the gene or the subsequent transcription? Multiple studies indicated it was the later with the transcriptional factor (a protein needed to kickstart transcription) binding to the DNA sequence before methyl groups bind to the DNA sequence. 

 This would make it possible that the state of DNA methylation is a marker for a particular condition. If proteins are being expressed correctly and causing a disorder, the absence or presence of methyl groups  can tell you what proteins are being overexpressed or under expressed and can also help devise new treatments. For example, techniques to add or remove the methyl groups or techniques to reduce the impact of the protein.

 However, it is also possible that the methylation of DNA plays a critical role in the pathophysiological mechanism in transcription. This basically would mean that methyl groups binding or not binding to the DNA sequence would set off a chain reaction, affecting the transcription of proteins - potentially causing disease.

So what does this actually have to do with CRISPR? 

CRISPR Cas9: The molecular biologist’s dream team.

CRISPR stands for clustered regularly interspaced short palindromic repeats and was  first discovered in the E.coli genome in 1987. It refers to an immune system that bacteria species use for defence against re-infection. Essentially, the bacteria can use CRISPR to create a memory of the infection, stopping it from being infected again.  Unlike the human immune system, the ‘memory’ created by CRISPR is passed onto the next generation.

It is made up of the following components- the Cas9 nuclease,  a type of enzyme that cleaves DNA and RNA,  and noncoding guide RNA (gRNA). RNA is similar to DNA but it is single stranded, whilst DNA is double-stranded, and contains a different sugar in its make-up. Its most important role is to get information transferred from DNA to its required location. It's often referred to as a messenger. 

This guide RNA has a target-specific CRISPR RNA (crRNA) and a trans-activating RNA (tracrRNA). The crRNA  consists of a 20-nucleotide (a nucleotide is an individual component of a DNA molecule) guide sequence and a partial direct repeat.

The guide RNA directs the Cas9 nuclease to a specific place in the genome- and causes a double stranded break (DBS) at the selected location. In other words, this is a cut in both strands of the DNA- at the same location.

But why would we want to induce double stranded breaks in the DNA?

Inducing a DBS causes DNA repair systems to kick in to repair the double stranded break. It is possible to exploit these repair pathways to manipulate the genome at the selected locus. The broken strands will undergo one of two major pathways to repair the DNA damage: Non Homologous End Joining (NHEJ) or Homologous end repair (HDR).This repair pathways can lead to the insertion or deletion of DNA- otherwise known as 'indels'. 

                                                                        Genome Editing using CRISPR Cas9. 

NHEJ works by the ends of the DSB being processed by DNA repair mechanic, and re-joined. As a result it can scars in the form of indel mutations- insertions or deletions. It is error prone due to the generation of indel mutations but can be harnessed to mediate gene knockouts   In comparison, HDR is only really active in dividing cells and varies in efficiency based on the cell type, repair template and genomic locus. Generally, it works by creating a repair template. This template can be double stranded DNA with ‘arms’ flanking the sequence to be inserted, or in the form of single stranded DNA oligonucleotides. 

This has multiple applications for healthcare. Being able to induce an indel into DNA can result in a disease-causing gene being knocked out. Due to the nature of DNA always using triplet nucleotides to generate a protein, adding in extra DNA or removing DNA gives extra or less nucleotides. This ruins the sequence of triplets, stopping the protein from being produced. This is known as a protective mutation.  CRISPR also shows use in treating disease caused by viruses by being able to cleave viral DNA. Viruses rely on certain sequences of DNA being able to hijack human DNA to create more copies of itself, causing disease. Cleaving the viral DNA stops it from entering the human DNA and stops the disease. 

It is also possible to use CRISPR to introduce desired characteristics. In 2018, He Jiankui announced that he had used CRISPR Cas9 to edit two human embryos, making the babies less susceptible HIV- the CRISPR cas9 disrupted a gene that codes a protein which allows HIV to enter immune cells. He Jiankui was sentenced to three years in prison in 2020.

But the technique is not just for genetic engineering. This is seen by Sapozhnikov and Szyf using CRISPR cas9 to find the answer to a question that has been plaguing molecular biologists for decades. 

The ultimate showdown: CRISPR against the gang- TALEN, ZFN and RNAi

TALENs–transcription activator like effector nucleases are able to cut DNA sequences of interest, producing a DBS with high frequency and are derived from bacterial proteins. A similar nuclease, ZFN or Zinc finger nucleases are derived from a transcription factor found in Xenopus oocytes. These aren’t as efficient or specific as TALENS but work in a similar way; a nonspecific domain of DNA is fused to a sequence-specific DNA binding domain, generating double stranded breaks.

With both ZFNs and TALENs, it is possible to customise the DNA binding domain, meaning it can recognise virtually any sequence.  DNA is full of highly specific sequences, with each one meaning a different thing. Being able to programme the DNA binding domains means the ZFN and TALENs can cut anywhere. CRISPR on the other hand relies on PAM sequences. PAM refers a short sequence that Cas9 has to bind to before it can cleave DNA. 

However, what gives CRISPR an advantage over ZFN or TALEN is how simple and quick it is. When using TALEN, a new complex clone has to be designed for each DNA target, whilst if using ZFN, artificial proteins with customizable sequence specific domains have to be generated. This is not an issue with CRISPR; one invariant Cas9 nuclease can be targeted to a large variety of DNA motifs.

Meanwhile, RNA interference (RNAi) was the ‘magic bullet’ for gene targeting, provided the DNA sequence was known first. As the mechanisms for this became apparent, it was soon used in human cells to inhibit genes. However, an issue with RNAi is that it didn't always cause a complete knockout- the gene could still be active, just at a lower level. This is not an issue with CRISPR Cas9 as it usually allow for a complete knockout of genes.

Dead but not necessarily inactive.

What Sapozhnikov and Szyf did slightly differently was to use a nuclease-dead Cas9, along with the guide RNA. This is also known as a nuclease-deficient Cas9 or dCas9.  This basically meant that it didn't have the nuclease enzyme. This is actually a lentiviral system created by Liu et al in 2016 to determine whether an inactive nuclease would cause or erase DNA methylation.

The use of a dead Cas9 is a slight variation on the classic CRISPR /Cas9 system that prevents the formation of the double stranded break but still allows for RNA-guided targeting. As a result, Sapozhnikov and Szyf did not actually alter the DNA sequence- as is commonly seen in CRISPR.

CRISPR vs TET.

Of course, what was also important in their experiment was the decision not to use of TET-based epigenetic editors. TET enzymes can either inhibit methylation by replacing a methylated cytosine with  a unmethylated cytosine.

However, Sapozhnikov and Szyf chose not to use TET. They instead used CRISPR/dcas9 for targeted methylation- i.e. using the system to add methyl groups. They proved that Cas9 can add methyl groups to DNA itself .

However, they did decide to assess the efficacy and specificity of the Liu et al system. This was to give them an accurate idea of the limitations of available targeted DNA methylation editing technology. So, Sapozhnikov and Szyf fused a dead Cas9 to the catalytic domain of a TET enzyme; TET1- which promotes active DNA demethylation.

CRISP(R)-ing up the Methylation.

Sapozhnikov and Szyf used the dead nuclease and guide RNA to target specific sites in the DNA. The DNA they chose to use was the interleukin-33 (Il33) gene, due to the presence and location of the CpG islands.

By removing a methyl group, a gene can thus be un-silenced and can be transcribed.

What they found out is as follows:

Cells that were exposed to the TET enzyme were more demethylated but did not have an adequate guide RNA. In comparison, the cells that were not exposed to the TET were less demethylated but had a better guide RNA. This basically mean that using TET didn't cause a complete 'on-switching' off the gene but did make the system more accurate.

The demethylation caused by using a dead Cas9 and TET1 was spread along a ‘substantial’ genetic distance. For example, in some cells, CPGs located 700 bp away from the target region were demethylated. This suggested that demethylation is not a tightly regulated process, raising questions about the role of methylation in transcriptional changes. Transcription has to be incredibly accurate and accurate, so anything involved in causing it would also have to be accurate. 

Using a dead Cas9 along with dead TET resulted in demethylation and transactivation of the Il33 gene to comparable levels with dCas9 TET. This meant that the IL33 gene became activated to the same extent in both of these systems. But the system with the dead Cas9 and dead TER lacked any capacity to initiate the active DNA methylation process. This means it is not clear how the transcription of the Ill33 took place, considering that the methylation should not have been possible.

They were also able to determine that demethylation is not the only epigenetic change conferred by dCas9-TET- this was as an increase of 5-hydroxylmethylcystoine was detected when the promotor was exposed to dCas9-TET but not when exposed to dCas9-deadTET. 5-hydroxylmethylcytosine refers to the molecule formed when the 5-methylcytosine is oxidised by TET enzymes and it is believed to be linked to the control of DNA methylation.

As it has been found that dcas9-dead TET is capable of activating transcription, this means catalytic 5-hydroxylmethylcytosine is not necessary to begin transcriptional induction.  This raises questions on what is actually needed to begin transcription.

CRISP(R)-y Ethics.

Anything involving genetic engineering will have ethical concerns that will need to be addressed and CRISPR is no exception to this.

One ethical concern that has to be addressed is the morality of enhancing the germline-i.e. the cells that will be passed down to future generations. It is entirely possible to use CRISPR to make the next generation ‘better’ than the first- as seen in the film Gattaca.

                                                                      He Jiankui: the creator of the CRISPR babies. 

He Jiankui, a Chinese scientist, edited the DNA of two babies to protect them against HIV. If this is allowed, will parents wish to ‘protect’ their children against other conditions? Will this bring us closer to the future seen in Gattaca?

It has also been noted that CRISPR can have negative impacts. In a recent study conducted at Kathy Niakan of the Francis Crick Institute, 22% of genome-edited embryos had unwanted changes- including DNA rearrangements and large deletions of thousands of DNA letters. Dieter Elgi in New York City also led a study where CRISPR resulted in large segments of the relevant chromosome being lost. These changes were completely unpredictable. This seems to indicate that there is still quite a bit that needs to be understood about the CRISPR technique- perhaps it is not as accurate as hoped. So it has to be asked whether it is ethical to alter the genome when there is still so much that is not quite fully understood.

However, the potential of CRISPR Cas9 in curing disease must also raise the question whether it is ethical and moral to deny the life-saving work of CRISPR. For example, CRISPR Cas9 can be used to treat melanoma, sarcoma, and myeloma, by expressing and switching off receptors associated with the immune system and the cancer cells. There is also no doubt that CRISPR can be used to treat genetic disorders, such as Cystic Fibrosis and Sickle cell disease. Could CRISPR be the only hope for many people?

CRISP(R)-y Methylation: The future.

Sapozhnikov and Szyf have potentially raised valuable questions about the relationship between DNA methylation and transcriptional genomics but may also have validated the use of CRISPR to control transcriptional regulation and expression.

If it is possible to control methylation, using the system that Sapozhnikov and Szyf adapted from Liu et al, why not use it as a form of genetic engineering? For example, if DNA demethylation can activate a gene previously silenced, could this result in a transcriptional change that could protect against disease? A benefit with DNA methylation is that it is possible to reverse the changes made- for example, using TET enzymes.

This is why it is important to determine what causes methylation and whether methylation is responsible for transcriptional changes.  It provides an alternative form of genetic engineering that many may consider to be more ethical than CRISPR/cas9 would be.

As for the future of CRISPR Cas9 itself, CRISPR appears to one of the most advanced and most brilliant techniques currently available for genomic editing. However, it is not impossible that more advanced genomic editing technologies will be developed. Many would not have believed that something more advanced than RNAi could ever be theorized.  

There is little doubt that genome editing will become more accessible and more acceptable as understanding of the genome and the increases. Whether it is CRISPR that will take to us the best possible embryos as seen in Gattaca remains to be seen.

Scisimplifalse- That's not QUITE how science works: When over simplification causes problems

In my previous article, I gave some examples of public icons that were samples of what I call 'Scienstupidity'. Whilst these guys have made incorrect, inaccurate and just plain stupid comments, there is also another band of comments that I am looking at today. This what I have decided to call 'Scisimplifalse'. Those technically correct statements and comments about a scientific fact or development, but simplified to such a degree that it becomes misleading, Honestly, I think that these kind of comments and statements cause more damage- to both people and science as a whole.

First up, the delightful James Watson. This guy came up recently on some other blog posts I did discussing his awful comments on just about anything. 

In 2007, Watson told a British newspaper that he was "gloomy about the prospect of Africa" as their "social policies are based on the fact that their intelligence is the same as ours whereas all the testing says not really"  He then doubles down on this by stating that whilst we might want all humans to have the same genetic-given intelligence, "people who have to deal with Black employees find this is not true". What Watson is suggesting here is that genetic testing  is showing that African people do not have the same intelligence as 'ours'. This is apparently shown by Black employees. So what he is essentially suggesting is that genetics affects intelligence and Black people have apparently not inherited the genes that control intelligence.  This is not a misquotation or him being taken out of context- the same 'theories' are suggested in his 2007 memoir "Avoid Boring People: Lessons from a life in Science". Lovely title. In addition, he wrote that "there is no firm reason to anticipate that the intellectual capacities of peoples geographically separated in their evolution should prove to have evolved identically". In other words, people evolved different genes and this resulted in different 'intellectual capacities'.  He also suggested that genetics could be the reason for 'the imbalance in the representation of men and women in science' - implying that women are genetically less intelligent that men. In 2019, Watson confirmed that he still held these views.

Okay. Lets look at the science. Do genes control intelligence? Well, yes and no. 

There is a key concept when it comes to genetics and that's the idea of nature vs nurture. There are some characteristics that can be controlled by your genetic code and your environment, whilst some traits are controlled only by genetics.  Something as abstract as 'intelligence' with multiple different meanings has NEVER been proven to be caused by only one or the other. 

Genes can be LINKED to intelligence- some versions of genes (alleles) have been studied and may- I repeat MAY, be linked to an increased IQ. Inheritance of intelligence is estimated to be about 50%- this basically means that genetics only explains half of the variation in intelligence between parents and their child. For example, if a child was judged not to be as smart as their parents, and 100 explanations were suggested for why this was the case, only 50% would be genetic- based.

 In one 2017 study by lead author Suzanne Sniekers (et al) and published in the journal Nature Genetics, 52 alleles were implicated in intelligence, with these genes being mostly expressed in brain tissue. But this only explained up to 4.8% of the variation of intelligence seen -in other words, if you had 100% people, less than 5% of them could be classed as more intelligent purely because of their genes. The study also noted that when comparing all the implemented genes with the variance in intelligence, they could be responsible for a 1.9 fold increase. This means that if a person had all of the 52 alleles, their intelligence could be double someone who didn't have any of those alleles.  BUT, it's unlikely that a person would inherit all of those specific alleles. The study also didn't make it clear what they meant by intelligence- which is honestly such a vague term. Most of these intelligent and genetic studies use IQ - which is now argued to be outdated and doesn't measure cognitive abilities accurately.   Intelligence can also be about verbal comprehension and spatial visualisation, as well as creativity and social intelligence. 

You can also argue that differences in intelligence are more to do with differences in resources than your genetic code. For example, lets say kids at a private school score higher in their exams than the local secondary down the road. Are the private school kids any more intelligent than the local secondary school Probably not- but they are provided with more resources. Other factors that have been known to increase intelligence are parenting, healthcare and nutrition. A child, no matter their genetic code, can reach their full potential if they are surviving from illness and are not eating properly. 

So in short, James Watson wasn't completely and utterly wrong here. There was a fragment of truth in what he was saying.  Genes do have a role in intelligence which can't be denied. But to imply deliberately or otherwise that genes are the only controlling factor in intelligence- without actually defining what he meant by intelligence, makes his statement completely inaccurate and misleading, as well as totally offensive. 

Next up is Richard Dawkins. This one is actually a bit pedantic in my opinion as most scientists would hopefully know what he meant but he did unintentionally cause some confusion and debate. 

 In his book, 'The Selfish Gene',  Dawkins stated that genes were 'selfish'. When taken in context, Dawkins was talking about how a gene that influences whether it will be inherited or not, will become more common in a population. For example, if one version of a gene produces more of a hormone that increases fertility, as opposed to another version of a gene that produces less of the hormone, the one that increases fertility will most likely be passed on. Dawkins pointed out that one allele of the Segregation Distorter (SD) gene complex in fruit flies results in sperm that don't have this specific allele dying, so only sperm containing the mutated SD survive. This reduces overall fertility but increases transmission of this SD. Hence, 'selfish'. 

Dawkins was not wrong in this theories but the problem we have here is that Dawkins has used metaphorical and simplistic language that was misleading when taken out of context. He seems to imply that genes are capable of conscious thought and directly influence behaviour-i.e. making someone selfish.

It opens up another question. Do genes control behaviour? Well, not directly. Genes are responsible for the production of proteins, and some of these proteins are needed for brain development, as well as hormones. These biological systems are what influence behaviour. Problems with these systems, caused by proteins can change behaviour -i.e. MAOA is needed for the breakdown of neurotransmitters such as serotonin. So, mutations of MAOA can alter levels of neurotransmitters which may alter behaviour. But as in the previous example, the environment also plays a role.

Funny how the first two examples of Scisimplifalse have involved genetics. It's a relatively new field in science and its rapid expansion  and potential means its inevitably prone to a lot of misinterpretation. But moving away from genetics, up next is Elon Musk.

In December 2021, Elon Musk tweets that SpaceX is starting a program to turn C02 from the atmosphere into rocket fuel, and inviting people to join. 

Okay. He's not actually that wrong here- CO2 CAN be used to generate fuel. But Elon Musk makes this process seem a lot more simplistic than it actually is.

To turn CO2 from the atmosphere into fuel, the first thing you need to do is get the C02 in the first place- for this, you need a process called Direct Air Capture. This is extremely expensive and needs a lot of energy. Where could you get the energy for DAC? Possibly by burning fossil fuels... which leads to C02 being released again.

Once you have the C02, you must then react CO2 with hydrogen. This process will give you water and methane- a viable rocket fuel. Also a natural gas. Which you can find naturally or produce in quite a few other ways. To get it from C02 plus hydrogen, you will require a whole load of energy and to be flippant, a whole load of money. But I suppose someone like Elon Musk doesn't need to worry about the finance side of things. 

In summary, Elon Musk seems to be implying that we can easily get rid of CO2 by converting it to rocket fuel. Well, you can produce 'rocket fuel' if you have big enough pockets, but you aren't making anything particularly unique. You probably aren't getting rid of any C02 either- you're probably burning more in the process.

Last one on this list is Dominic Lawson, a British journalist and columnist. In March 2006, Lawson writing for The Independent, made the following statement.

 “The UK contributes only 2% of global CO₂, so cutting our emissions has no statistically significant effect on the future of the world's climate". 

Okay, the statistic that Dominic Lawson presents here wasn't - and still isn't, actually wrong. As of 2024, it has been suggested that the UK now contributes less than 1% of global C02 seems to imply that the UK shouldn't really be bothering about getting to net zero. This is just wrong. When we consider each person's individual carbon footprint, we will find that as of 2023, the average British person is responsible for 4.4 tonnes of C02 per year. The global average of C02 emissions per person is 4.8 tonnes. As the UK makes up 0.84% of the population, this also gives the UK a lower share in global C02. 

But the statistic has been coupled with a statement that is completely oversimplified. Lawson seems to imply that we shouldn't be bothering so hard to get the UK to net zero, because it won't have any impact on climate change. The idea of net zero carbon has been quite prominent and what it means is that the total amount of C02 added to the atmosphere is equal to the amount removed from the atmosphere. It's not attempting to stop C02 emissions completely- its just aiming to have a zero net impact.  

This statistic completely ignores the fact that UK consumption of C02 is reliant on goods manufactured abroad. For example, if the UK outsources production to China, the emissions from this production are counted as part of China's carbon footprint- and not the UK's. So, the "2%" figure is shifting responsibility elsewhere and the real figure- the total emissions that the UK is ultimately responsible for, will be higher. 

What Lawson also seems to forget is that climate change is not about who is producing the most right now.- it's about who emitted and who can reduce emissions. Climate change is not going to skip countries because they didn't emit as much as the one next to it. The impact of C02 emissions is global - everyone has and is contributing to the total C02 in the atmosphere. It's also worth pointing out that the UK was one of the top historical contributors due to the Industrial Revolution. The UK was actually one of the first to start emitting C02 on a large scale. So it's a bit rich to try and be shirking responsibility.  

Logically, if everyone thought like Dominic Lawson seems to want us to think, then no country will ever make any effort to reduce their C02 emissions. The UK does still have some influence in  international climate leadership and can be trying, in want of a better, less twee phase, can set an example. The UK is developed enough and has enough ability - and responsibility to be cutting emissions. 

The danger of these comments and statements is that they appear to be true. They are backed up with valid statistics- and they are presented by people who are on the whole well-known in their fields.  Every article with James Watson featured will present him as the man who 'discovered DNA' or maybe the man who 'co-discovered the structure of DNA'. No one ever mentions that James Watson didn't really make any other major discoveries after this- or that the majority of the DNA structure research had been done by others.  But point is, it makes him sound important, and intelligent  which has the problem of making him somewhat influential. 

 The majority of people can roll our eyes at Donald Trump and Jennifer McCartney- I would hope that the majority of people can accept that they really don't know anything when it comes to scientific developments and facts. But when a well-respected scientific or public figure makes a point that seems logical and that it could be correct, it becomes a great deal harder not to believe it. For example, most people with a modicum of intelligence (genetically linked or not) can work out that injecting disinfectant is really not a good idea, but when someone is able to present some statistics and a seemingly sensible point... well, that's where the damage starts. Unfortunately, there isn't an easy way to fix this said damage. Humans appear to like sensational statements and it is much harder to get someone to STOP believing than getting someone TO believe. 

Scienstupidity- That is not how science works: stupidity when talking science!

Science can be confusing. There are many developments going on and it's hard to keep track of it all. No one expects everyone to be an expert in every aspect of scientific theory and fact. That said, there are some things in science that are just plain wrong. What I find rather amusing is when a public figure states something that is just so wrong thinking that it is completely right. I then find it extremely horrifying when these statements end up causing so much harm. 

One example of an ignoracle causing damage by stupidity when talking science is the wrongvangelist Donald Trump. It isn't exactly ground-breaking to suggest that this guy just doesn't understand science -at  all. I'm not even sure if I can make 'science' more specific. Does he not understand immunology? Does he not understand earth sciences? Or is this just science in general. Sadly, I think the latter. 

Donald Trump hit headlines when he made a comment in April 2024 about injecting disinfectant to combat COVID-19 His exact comments were "And then I see the disinfectant where it knocks it out in a minute. One minute. And is there a way we can do something like that, by injection inside or almost a cleaning?" I don't really think I need to go into why this is not just incorrect science, but also plain stupidity but I guess you never know... Disinfectant breaks down cell walls, causing microbes to rupture. They also damage cellular proteins and stop them from replicating. Humans also have cells that contain microbes and cellular proteins. So if humans were to inject disinfectant to treat COVID, it would, to be fair, 'knock it out' … but it would cause a load of damage to their own cells! To my horror and my despair for humanity, at least five states in the USA reported a sharp increase in calls to poison control centres after people started ingesting bleach. 

In September 2025, Donald Trump also claimed there was a link between Tylenol (paracetamol) and an increased risk of autism. According to Trump, taking Tylenol during pregnancy 'is not good' and 'can be associated with a very increased risk of autism'.  Horrific grammar aside, this is just complete and utter crap.  There has been an increased rate of autism diagnosis in the last 30 years; in the UK alone there has been an 787% increase in ASD diagnosis between 1998 and 2018. However, experts worldwide credit this to increased awareness, increased testing and an expansion in the condition definition. Autism used to be a disorder only affecting children with severe language and intellectual disabilities. It is now a much wider spectrum that includes milder social- communication differences. 

There WAS a 2020 study published in JAMA Psychiatry that suggested a link between a higher 'acetaminophen burden'  and higher odds of ADHD, ASD and coexisting ADHD and ASD. Acetaminophen is the main component of paracetamol. But crucially, this study was only an observational study- which basically means, that the researchers watched to see what would happen. There was VERY limited evidence  that the acetaminophen alone was causing anything and even the authors stated that the data they generated 'warrant additional investigations'. They also pointed out that they did not have a group that had not been exposed to acetaminophen possibly biasing the results. 

Laurie Tomlinson, from the London School of Hygiene and Tropical Medicine also pointed out that the study seems to ignore why paracetamol was taken by the pregnant women. She noted that women with hypermobility may need to take paracetamol for joint pain but are more likely to have children with ASD due to links between the two conditions. In addition, a Swedish study of 2.5 million children born between 1995 and 2019 did not find any association between risk of autism, intellectual disability or ADHD and pregnancy. It is still too soon to know how much damage this will cause to prenatal care and the neurodiversity community. 

Another aspect of science stupidity that causes an incredible amount of damage is the 'vaccines cause autism' dumbacle and we can partly thank the nonsensical blather that Jenny McCarthy comes up with for making this ignorama even worse.

Jenny McCarthy

I can't believe that I'm writing this in 2025 and I wasn't even going to bring it up because of the drama it causes. But I can't have an article about stupid scientific comments and not bring the vaccines and autism debacle. Many people do believe in this quackery (there's another rhyming word that I would like to use but I will refrain) but Jenny McCarthy is one of the world's best known. According to McCarthy, her son  was diagnosed with autism at 2 1/2 years old after receiving the measles, mumps and rubella  (MMR) vaccine. She said that her son had been previously hitting all milestones but about a month after the MMR, he was having seizures, bloating, eczema and constipation - conditions that are 'comorbid' with autism. To be fair to McCarthy, she stated that she didn't think it was 'just' the MMR vaccine that 'triggered' the autism, and that it was to do with a child with autoimmune disorders receiving so many injections.  

Okay, there is a link between autism and autoimmune disorders. There has been some evidence suggesting that certain gene mutations linked to the immune system have some links to ASD. This is not to say that these gene mutations will DEFINATELY cause autism. For example, a 2007 study in Portugal found 4.2% of children with ASD had a mitochondrial respiratory chain disease which can affect the activity of the immune system. So, it is completely possible that McCarthy's child did have autoimmune disorders. If these disorders were linked to genetic mutations, then yes, her son MAY have had an increased chance of autism. 

But to make one thing clear...

VACCINES DO NOT CAUSE AUTISM!!!!!

This whole imbroglio comes down to Andrew Wakefield, who, at the time, was a British surgeon. He has seen been struck off. In 1998, he and 12 colleagues published a case series in the Lancet - a prestigious medical journal, suggesting that the MMR vaccine may cause developmental disorders and behavioural regression in children.  There were immediate problems with the paper, the first one being that only 12 children had been investigated. For those who aren't familiar with how scientific studies are carried out, 12 is a RIDICULOUSLY small sample size.  Sample sizes need to reflect how widespread a condition or factor actually is. It's like picking up a handful of three-leaf clovers out of the billions of them around and stating 'four-leaf clovers don't exist'. We know four-leaf clovers exist but we also know they are rare. Likewise, 12 researchers might be able to hunt down 12 four-leaf clovers and present them saying 'all these clovers have four leaves and they were all exposed to sunlight. Therefore, sunlight causes four leaves'. 12 children having 'behavioural regression' and having had a MMR vaccine means virtually nothing. Later, Wakefield was charged with fraud, having picked the data that suited him - literally picking the four leaf clovers. He claimed that all 12 children were 'previously normal' - medical records showed that five of them had documented development concerns before receiving the vaccine. He also claimed that nine of the twelve children had 'regressive autism' - only one had been diagnosed with this. 

Andrew Wakefield

He also made up a condition; 'autistic enterocolitis', a gut pathology that he claimed was present in autistic children and may also be associated with the vaccine. But when these children's colonic biopsy samples were reviewed, the hospital's chief pathologist judged them as 'unremarkable' - i.e. totally normal.  I think this is where the lines between fact and fiction blur a bit when it comes to autism and vaccines. There MAY be a link between the gut and autism, with ASD children often experiencing gastrointestinal problems. It's not really known that Andrew Wakefield also suggested that the MMR vaccine caused gut problems even though its not true. If a person finds information about the link between the gut and autism, and then comes across information suggesting that MMR causes gut problems- without knowing that this link was fraudulent, its not improbable that they can leap across to suggesting MMR causes autism. WHICH IT DOESN'T.

There are many more examples of stupidity when talking science that I could bring up, but that would result in me ending up writing a whole novel. These examples are the ones that I think are the stupidest and also the most harmful to the human race. I'm honestly hoping that an anti-vaxxer might read this blog and decide to do a little more research- although I'm not so arrogant to think that my crazy eccentric blog will convert anyone to a new way of thinking!

That's all from me this week!   

Jess x 

There be cells: tracing the history of the cell.

The most fundamental thing in biology is the cell. Nothing researched in biology makes complete sense without the cell. Yet this basic unit of life cannot be seen by the human eye and even viewed though the aid of a microscope, nothing about it at first glance gives much indication of how significant it is. So exactly did we find the cell and work out its significance?

Well, it all begins back in the 1600s.

The first time a cell was ever seen was by Robert Hooke.

Robert Hooke, 1680. 

 

Microscopes had been invented in about 1620 and in 1665, Hooke looked though a compound microscope, a simple act that had huge ramifications. 

A compound microscope uses two lens - an eyepiece and objective lens. The objective lens forms a magnified image which is then magnified further by an eyepiece lens. This gives much higher magnification than a simple microscope, using one lens, can give. Compound microscopes are still used in optical microscopes today, although with a much higher magnification than what was possible at the time. Remember, microscopes were not initially designed for cells- they were designed just for magnification.  No one had any idea how important microscopes would ultimately be.

 

 

 

 

How a compound microscope works. 

 

Hooke initially started with mundane human objects; he discovered tiny pores in thin slices of bottle cork and named them 'cells'. This after the latin word 'cella' which means 'small room' - used to describe the living quarters of monks, and also 'cellulae', meaning the sixth-sided cell of a honeycomb.

 

Hooke was reminded of honeycombs when looking though his microscope. 

 

 Hooke then looked at microorganisms - specifically the micro-fungus Mucor. His microscope - handcrafted and tooled in leather and gold can still be seen in Maryland.  Whilst beautiful, leather and gold are not practical tools for modern microscopes!

Hooke's microscope. 

 

Hooke made drawings of what he saw and had them published in 'Micrographia'. This was the first book to have illustrations of insects and plants seen through microscope. This publication inspired mass interest in the new field of microscopy. Samuel Pepys called the book 'the most ingenious book that ever I read in my life'. It is rather strange to think that cells, one of the most important and essential aspects of biology, were discovered a year before the Great Fire of London. For context, many people in this time could still remember the beheading of Charles I! 

Hooke was not able to see any internal components of the cells- like nuclei and had no clue that these' cells' were alive. The magnification needed for this was not advanced yet and it would take a few more developments in microscopy before that was possible. In fact, being able to include that cells were indeed alive happened in Hooke's lifetime. 

Robert Hooke's drawing of 'cells' in cork. 

 

Less than 10 years after the publication of Micrographia in 1665, Anton van Leeuwenhoek, was able to take advantage of the improvements in microscopes.  In 1676, Leeuwenhoek became the first to notice that the cells were moving- and therefore must be alive. He described many forms of microorganisms, which he named 'animalcules'. He saw bacteria and protozoa, a type of single-celled organism that feeds on organic matter.  He was also able to accurately describe red blood cells. Crucially though, he was the first to see sperm cells of humans and animals and saw that reproduction would require the sperm cell to enter the egg. This allowed for the prevailing theory of spontaneous generation to be put to rest.  Hooke confirmed his observations.  This was also the first time that cells in animal tissues could be seen- they are much more fragile than plant cells.  

Antonie van Leeuwenhoek, after 1680

 

Moving onto 1804, Karl Rudolphi and Johann Heinrich Friedrich Link were able to prove that cells had independent walls. This suggested that cells were separate and distinct units; this laid the groundwork for the idea that organisms are composed of separate structural units. 

Karl Rudolphi

 

Johann Heinrich Friedrich Link. 

 

 

In 1824, Henri Dutrochet was the first to suggest that the cells were physiological units and that they were a fundamental element to the organisation of an organism. Henri Dutrochet was also the first to come up with the process of Osmosis; how water moves across a membrane. This theory is vital in understanding the physiological processes in cells, giving further information on how cells actually operate. 

 

Henri Dutrochet 

 

The work of these scientists all came together and allowed Theodor Schwann and Matthias Jakob Schleiden, with contributions from Rudolf Virchow to devise 'cell theory' in 1839. This theory suggested that every structural aspect of a plant and an animal were either made up of cells or resulting from cells. This also allowed them to include that the cell was the most basic unit of life.

Theodor Schwann

Matthias Jakob Schleiden 

 

 

In 1855, Rudolf Virchow was able to add to cell theory that all cells arise only from cells already existing. This had first been proposed by Robert Remak in 1852 who also suggested that binary fission was how animal cells reproduced. This marked the completion of classical cell theory. 

 

Rudolf Virchow

Robert Remak 

 

 

 

Of course, further discoveries that altered classical cell theory would be made later. However, classical cell theory altered biology for the better. It became clear that to understand life, scientists could no longer look at whole organisms or tissues and instead look deeper- the cell.  Looking closely at the cell gave rise to cellular physiology and also gave rise to modern biochemistry.

For example, in 1877, Wilhelm Pfeffer was able to propose the membrane theory.  This was gradually developed over time, with Ernst Overton suggesting that the cell membrane was made of lipids in 1899. In 1904, David Nathansohn added to this by suggesting the mosaic theory and Wilhelm Ruhland refined the mosaic theory to include pores in the cell membrane. Leonor Michaelis was then able to conclude the role of ions and demonstrated the membrane potential. All of this work was key in understanding how nerves and muscles work, as well as how cells transport vital minerals, vitamins and nutrients. This ultimately led to the first alteration of classical cell theory to modern; biochemical reactions and metabolic reactions occur within cells. It also became possible to add a second alteration; the activity of an organism depends on the total activity of independent cells. 

The mosaic model.

 

The discoveries that altered classical cell theory and turned it to 'modern' cell theory also revolved around DNA. In 1869, Friedrich Miescher first identified what was ultimately DNA. He discovered a microscopic substance that resided in nuclei - he called it nuclein. 

Friedrich Miescher 

 

In 1878, Albrecht Kossel isolated nucleic acid from nuclein and isolated its nucleobases- adenine, thymine, cytosine, guanine, and also uracil. In 1909, Phoebus Levene identified the base, sugar and phosphate nucleotide unit of 'yeast nuclei acid' -or as we know it; RNA. 

Albrecht Kossel

Phoebus Levene 

 

In 1927, Nikolai Koltsov suggested a 'giant hereditary molecule'. At this stage, he wasn't sure what this hereditary molecule actually was. It was Frederick Griffith in 1928 that came up with the first suggestion that it could be DNA carrying genetic information. 

 

 

Nikolai Koltsov 

Frederick Griffith

 

 

In 1929, Levene identified deoxyribose sugar in DNA and suggested it consisted of four nucleotide units linked together through phosphate groups.

In 1933, Jean Brachet suggested that DNA was found in the cell nucleus, with RNA in the cytoplasm. In 1943, Oswald Avery, Colin Macleod and Maclyn McCarthy devised the transforming principle, suggesting how bacteria are capable of transferring genetic information. 

 

Jean Brachet

 

Oswald Avery

 

Colin MacLeod

Maclyn McCarty

 

By 1951, Alec Todd suggested how the backbone of DNA is structured, which played a crucial role in the work of Franklin, Wilkins, Watson and Crick. In May 1952, photograph 51 was born and in 1957, Crick devised the central dogma describing the flow of genetic information. In simple terms; DNA makes RNA and RNA makes proteins. 

 

Alex Todd 

 

In 1958, the Meselson-Stahl experiment was done. In the same year, the discovery of codons allowed for Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenburg to decipher the genetic code. Codons are the triplet DNA bases that give specific amino acids. 

Har Gobind Khorana

Robert W. Holley

Marshall Warren Nirenberg, 2002

 

With this, the molecular age of cell biology had officially began--and this led to some more adjustments to cell theory. The modern theory, still in play, now has seven tenants:

1.All known living things are made up of one or more cells.

2.The cell is the basic unit of organisation and function - all the vital functions of an organism occur within cells; including metabolism, energy, and DNA synthesis 

3.All living cells arise from pre-existing cells; cells have to divide which requires replication of DNA.

4.Cells contain DNA which is found specifically in the chromosome and RNA which is found in the cell nucleus and cytoplasm. 

5.All cells are similar in chemical composition and metabolic processes; including proteins, lipids, carbohydrates and biochemical pathways.

6.Specialised organelles-such as the nucleus, mitochondria, and ribosomes, perform distinct and essential functions with the cell.

7.Energy flow- metabolism and biochemistry occurs within cells. Cells are the site of energy transformation essential for life. 

This modern theory of cells was almost three hundred years in the making, starting with Robert Hooke in 1665, and being altered against in 1958.  Hooke's simple act of looking though a microscope can be said to have changed almost everything about biology - and it may still do so. Discoveries about cells and DNA are still being made on an almost daily basis. In another three hundred years, could more tenants be added and adjustments be made to the modern cell theory?