On Gain of Function Research

Corona viruses were first reported in 1965 in connection with research on viruses causing common cold.  Later  David Tyrrell pioneer in this field based on the then available data made a statement:  "Corona viruses cause acute, mild upper respiratory infection (common cold)"(1,2).    Ten plus years later  the   SARS  outbreak in 2003 with a case fatality ratio of 11% and   MERS, in 2017 with a case fatality ratio of  35%  forced scientists to reevaluate the coronaviridae family of viruses(3,4,). Because the causative agents, the  pathogens though  hitherto unknown to humankind,  were traced  to the corona family.   This  was also  like a wake up call,  to be alert and  prepared because there are lethal viruses lurking everywhere. A benign virus might have an hitherto unknown close cousin who might be pure evil.  Consequently  World Health Organisation's priority list of  diseases  that "pose the greatest public health risk due to their epidemic potential and/or whether there is no or insufficient countermeasures," included an X factor (5). 

The WHO document further stated that "Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease. The R&D Blueprint explicitly seeks to enable early cross-cutting R&D preparedness that is also relevant for an unknown “Disease X” (5).  (also see When Enemy is Unknown, this column Feb.2020).

So how do we enable early cross-cutting R&D preparedness to combat an unknown enemy?  That is where the tools of genetic engineering came in handy to the  scientific community.  Among other things  investigations began on  how a rather mild pathogen might  mutate to a dangerous  avatar  and  how a pathogen hitherto known only in  birds and animals might cross over  to humans (6).   Under the  innocuous label of  " Gain of Function Research",  scientists began  tinkering with the genes  of the existing viruses to make them  more lethal and/or contagious. Because this knowledge is essential to design effective countermeasures such as vaccines.   Naturally, GOF ( short for gain of function)  research triggered heated debates in scientific circles on the risks and benefits involved. Fear of possible laboratory leaks prompted many to shun and vehemently object to  GOF research.  True,  experiments are conducted in highly sophisticated labs adhering to stringent levels of biosafety. But still...   

Marc Lipsitch, professor of epidemiology at the Harvard  School of Public Health argued:  “Is this work so valuable for public health that it outshines the risk to public health in doing it?"(5) The debate reached  high pitch and high heat when scientists mutated the naturally occurring H1N1 bird flu virus  enabling it to be airborne and more infectious. There were other such scary  instances too. Of course all these  experiments were confined  in petridishes within four walls of  labs with very high biosafety level. Arturo Casadevall,  microbiologist at the Albert Einstein College of Medicine,  New York City, reassured everyone: “There is really no evidence that these experiments are in fact such high risk,” he said. “A lot of them are being done by very respectable labs, with lots of precautions in place.”  Nevertheless   the Obama government  clamped  morartorium  on GOF research in 2014 (6).   But it now appears that the research continued unhindered elsewhere.    The  moratorium was lifted  in 2017 and NIH, USA stated that  this line of research  helps us  to "identify, understand, and develop strategies and effective countermeasures against rapidly evolving pathogens that pose a threat to public health" (7) 

There are groups who insist that SARS-CoV-2,  the deadly virus responsible for COVID-19 pandemic is  a product of the GOF research, which somehow leaked out. The suspicion that  the SARS-CoV-2 is not a  natural pathogen but an engineered one , is due  to the detection of  an unusual   signature in its genetic makeup( 8).  A  natural predecessor from whom SARS-CoV-2 could have inherited this feature has not yet been identified either.  Then came the revelation of  the American links to the ongoing  GOF research projects at the Wuhan Institute of Virology, the epicentre of the COVID-19 pandemic (9).  This time, along with the dissenting scientists, public too  protested and demanded explanations. The  pitch rose so high that National Institute of Health, USA deemed it necessary to put out the following statement: "neither the agency nor its National Institute of Allergy and Infectious Diseases has “ever approved any grant that would have supported ‘gain-of-function’ research on coronaviruses that would have increased their transmissibility or lethality for humans."

Between 2014-2019, Wuhan Institute of Virology  has received  huge research funds from National Institutes of Health, USA.  Currently  this is being investigated. For the time being  NIH is  tightlipped  about the details, citing pending investigations (9).  Meanwhile speculations are flourishing.    But science is not built on speculations, we need concrete proofs.

TAILPIECE:

In brief:  The Road to hell is always paved with good intentions. 

REFERENCES:

1. Cold Wars: The Fight against the Common Cold: David Tyrrell and Michael Fielder,Oxford University Press 2002

2. Covid-19: First coronavirus was described in the BMJ in 1965 

3. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS)

4. MERS situation Update May 2021

5. Why Scientists Tweak Lab Viruses to Make Them More Contagious

6. US suspends risky disease research . 

7. NIH Lifts Funding Pause on Gain of Function Research

8. Natural and unnatural history of the coronavirus: The uncertain path to the pandemic  

9. Inside the risky bat-virus engineering that links America to Wuhan. 

Journey to the centre of the Earth

"That is Snaefellsjokull a mountain about five thousand feet in height, one of the most remarkable in the whole island, and certainly doomed to be the most celebrated in the world, for through its crater we shall reach the centre of the earth.”

The  Journey to the Centre of the Earth with Axel and uncle Otto is indeed an exciting experience.   Jules Verne published the French original in 1864 and later a new improved version appeared   in 1867. Since then the book has been translated into almost all languages, adapted to the big and small screens, made into video games, theme parks etc.  With a combination of  available scientific information of the day and fertile imagination  Verne wove  an  extraordinary   fiction.  Central to the theme  was the pure fantasy  of subterranean  volcanic  tubes which  facilitate  the journey.  Snæfellsjökull  glacier and adjoining areas have now been developed into  National Adventure Park by the Govt. of Iceland. 

Ever since its birth 4.5 billion years ago,  the Earth has gradually been cooling down, radiating  heat to space.    Analysing  the  magnetic records of ancient igneous rocks, scientists  detected  a sharp increase in the strength of the Earth's magnetic field between 1 and 1.5 billion years ago.    A "likely indication of the first occurrence of solid iron at Earth's centre and the point in Earth's history at which the solid inner core first started to "freeze" out from the cooling molten outer core", state scientists at the University of Liverpool.  

Structure of Earth

This cooling of the hot liquid outer core  and consequent deposition of iron crystals on the inner core is a  process in progress, though  extremely  slow.  The  inner core, 96% iron and the rest mostly nickel, manifests its presence  in myriad ways including  Earth's magnetic field and its rotation, but its existence could be detected  only in  1906, when  seismological measurements became possible. Since then  seismological wave propagation studies together with simulation and modelling  have  extensively been used to gain information about Earth's interior.  

The question  how   Earth's iron rich inner core which is hotter than the surface of the Sun remains a solid  is not yet fully  answered, though it is agreed upon that iron exists in some crystalline form.  Experimental observations that seismic waves propagate faster in the North-South direction than in the East-West direction suggest  a directionality for the core. The  most plausible,  generally accepted  answer is   the preferential alignment of the iron crystals with their long axis  along the rotation axis of the earth.   However that raises another the  question:  why  such preferential  crystalline alignment ?  Because the Earth's core is not growing uniformly, say scientists. The  east side under Indonesia's Banda sea is growing faster than the  west side under Brazil.  But  gravity quickly  evens out this discrepancy by aligning the crystals and restoring the spherical shape.  And here comes  the next question: why this lopsided growth?  Looks like we need to wait for answers and more questions.

REFERENCES:

1. Journey to the centre of the Earth : Jules Verne

2. Is Earth’s core lopsided? Strange goings-on in our planet’s interior?.

3. Lopsided Growth of Earth'sInner Core 

4. Dynamic history of the inner core constrained by seismic anisotropy. Frost, D.A., Lasbleis, M., Chandler, B. et al.Nature  Geoscience.  3 June.2021

5.

Harnessing Hydrogen

Tokyo 2020 Olympics was all set to unravel the  unique  achievements of Japan  in harnessing hydrogen energy. In fact the tagline of the Tokyo Olympics was  to be Hydrogen Olympics.  Japan was ready with its fleet of hydrogen powered vehicles, hydrogen refueling stations and   hydrogen powered athletes' villages. But unfortunately the event had to be called off due to the pandemic. But Japan is not disappointed. Tokyo Olympics was just one of the milestones in  Japan's roadmap  to  green eneergy.  Japan is bent upon  erasing its carbon footprints as much as possible  by  2050.  To reach  this final destination Japanese  academic and industrial research institutions  are working overtime , in close collaboration.  

Concept of a fuel cell

The energy content in 1 kg hydrogen is almost equivalent to 1 gallon(~ 2.8kg) of  gasoline. The concept of hydrogen fuel cells was demonstrated way back in 1932 and since then has been  tapped in  limited edition applications.  In its simplest form an hydrogen fuel cell consists of anode and cathode separated by an electrolyte. Hydrogen is introduced at the anode and air/oxygen at the cathode. At the anode a catalyst  splits  hydrogen atoms  into protons  and electrons. The protons move through the electrolyte  towards cathode, combine with oxygen and form water.  Electrons flow through the external circuit generating an electric current.   Simple though it is,  there are several complex technical challenges to overcome to make the process commercially feasible. Challenges begin   from the  primary production stage to  storage, transportation, delivery and ultimate use. 

Hydrogen is abundant in nature but is always  in chemically combined form such as in water or in hydrocarbons. Hence it is necessary to have cost effective processes to strip hydrogen free. Then comes the storage needs. While for on-site applications, perhaps hydrogen can be stored in gaseous form, for long distance distributed applications  appropriately designed network of  gas pipelines is necessary. That calls for huge investments in infrastructure development.  Storage and distribution as  liquid  hydrogen is another possibility but requires cooling the gas to  -263 degC making it  an energy intensive, expensive process.  Fixing hydrogen gas as ammonia  is often preferred because  ammonia is easy to liquify and transport, and later hydrogen can be reclaimed through   catalytic cracking  of ammonia.  

Chiyoda Corporation  believes in  Energy and Environment in Harmony. Scientists and Technologists at  Chiyoda have come up with a more attractive alternative.  They  have perfected the technology of reversibly  hydrogenating toluene to methyl cyclohexane (MCH) using  platinum nanoparticles as catalysts. The advantage with MCH is that the existing petroleum refinery set up and associated storage/distribution network system could be used as such with minimal modification. That spells a huge saving.  In April 2020 Chiyoda  joined hands with  Mitsubishi Corporation, Mitsui & Co. Ltd. and NYK Shipping Line  and   transported MCH produced at  Darussalam, Brunei  to Kawasaki refineries in Japan. In fact  Kawasaki  is   involved in all 4 stages: production, storage, transportation and utilisation. While Mitsubishi  is  experimenting with  hydrogen gas turbines,  ENEOS, the mammoth energy company will be setting up hydrogen refilling stations for automobiles.  Japan is dead serious about  its Mission Hydrogen. It has even set a target price  of  US$ 2.0 per kg by 2050.   

Tailpiece:

In the meanwhile hydrogen is getting color-coded  depending upon how it is produced. 

   

Grey Hydrogen:      Natural gas is split into hydrogen and CO2   .  Hydrogen is collected and                                          stored, but CO2 is let out into the atmosphere.  This is the current process.

Blue Hydrogen:       Process is the same as for Grey Hydrogen but CO2 is  not let out into the                                      atmosphere but fixed in appropriate manner.

Green Hydrogen:     Hydrogen is produced by electrolysis of water using energy from a                                                combination of  renewable resources such as  wind and solar 

Pink Hydrogen:        Electrolysis of water using  nuclear power.

Yellow Hydrogen:     Electrolysis of water using exclusively  solar power.

REFERENCES:

1. Focal point : Hydrogen Energy in Japan : Nature 25th March 2021

2. Alternate Fuels Data Centre

3. Transitioning to hydrogen

4. Australia's pathway to $2 per kg hydrogen

5. The hydrogen color spectrum 

Secrets of Mariana Trench

Percy  the Martian rover  is  currently  having a field day, literally.   Already it has sent 13,854 images  and  recorded an audio  of itself  driving  around  on the Martian landscape.  Based on the information received so far, indications are that there could be water  trapped  under he Martian crust. A great feat indeed.   Percy's three dimensional measurements are equally impressive:  weight 1025kg, height of 7ft, width  9ft and length  10ft.   And it is made of rigid, tough  material because the terrain it explores demands it. 

Mariana Trench Location  
courtesy Wikipedia

However Percy would be crushed and crunched if it ever attempted to explore the secrets of  Mariana trench. This is  the deepest  oceanic ditch at a depth of 11,000 meters.  Domain experts are of the opinion that the trench can submerge  Mount Everest  completely , with still a clearance of  2 kilo meters of water column above it.  The trench is not quite a touristic spot  what  with pressures upto 1000 bars and temperature below 4degC and total darkness. Initially it was thought that life as we know it couldn't exist  there  but later studies revealed that he trench  is home to  several marine species.   So  how do these species befriend  such hostile the conditions or more correctly how do they  adapt themselves?

pseudoliparis amblystomopsis 
courtesy: wikipedia

Deep sea investigators found  that Nature has played its evolutionary tricks to perfection. Studying the anatomy  of deep sea snailfish,Pseudoliparis swirei, researchers detected  several peculiarities. The  body is a bit gooey and the skull  is not in one piece but has a fractured  format perhaps to accommodate internal and external pressure differences The bones are not calcified  but are tender cartilages. In fact the species lack the gene for calcification altogether.  The snailfish is about 15-20cm in length yet  can withstand more water pressure than 1,600 elephants standing on its head says Mckenzie Gerringer  whose area of research is deep sea Physiology and Ecology .  

Taking cues from the anatomy of the snailfish, a team of Chinese scientists  have now designed a soft robot exactly like the original.   Pliable polymer silicon is used to shape the gooey  body with a  body length of 11.5cm and tail length of 10.5cm, and a wing span of 28cm. Muscles are made of dielectric elastomers(DE), which are smart electroactive materials that can produce strain.  Each DE muscle is equipped with a compliant electrode  inserted between two layers of DE sheets. Instead of packaging the electronics in a single printed circuit board, the team made a distributed array of several small  PCBs, gain a takeaway from the original. The team conducted field tests in Mariana trench itself, in South China sea as well as in deep lakes. The results are extremely promising.  It is expected that such soft robots will help us unlock the secrets of the deep sea.

Tailpiece  

The name Pseudoliparis swirei, is indeed a tribute to the memory of   Herbert Swire, a member of a British marine expedition team. In 1870, HMS Challenger carried this  team to explore the depths of the sea and they discovered the Mariana Trench.  Herbert Swire was the navigational sub-lieutenant  who kept an accurate journal and published it later.    

REFERENCES:

1. Life history of abyssal and hadal fishes from otolith growth zones and oxygen isotopic compositions.

2. Introducing Mariana Snailfish

3.Distribution, composition and functions of gelatinous tissues in deep-sea fishes: Gerringer et al

4. Morphology and genome of a snailfish from the Mariana Trench provide insights into deep-sea adaptation.  Kun Wang et al 

Cellulose Again

Cellulose chain courtesy Wikipedia

The  story of plastics actually began with cellulose,  way back during the last two decades of nineteenth century.   Cellulose,  isolated from wood pulp  was subjected to serious chemistry and Hyatt Manufacturing Company brought out celluloid in 1870.  This was cellulose nitrate  made  sufficiently pliable by adding small amounts of camphor.  But the material had a huge drawback; it was a fire hazard,  it burst into flames spontaneously  at the slightest provocation.  In fact its more popular name was gun cotton and often substituted for gunpowder.   Its meeker cousin cellulose acetate  was  synthesised by French chemist  Paul Schutzenberger.  The credit for taming cellulose acetate and unravelling several of its  useful qualities goes to two siblings Camille and Henri Dreyfus.  They found that cellulose acetate  could be made into neat protective films, spun into fibres,  and could also be injection moulded  into any desired  object.  In 1912  Swiss chemist Brandenberger perfected the art of making cellophane a thin transparent  film which revolutionised the packing industry.   But the golden period of cellulose plastics  was short lived.  The two world wars  demanded  cheaper, more versatile plastics  and the petrochemical industry generously provided cheap raw materials  for  the nylons, polythenes, polyesters, polyurethanes, polycarbonates etc.....  Cellulose was marginalised  for limited  applications.

Courtesy :wikipedia

In a recent comprehensive review   Tian Li and coworkers  highlight the need to relook at cellulose. They build a case particularly for cellulose fibres downsized to smaller free standing  fibrils. Such  microsized or nanosized fibrils  could be  made into  transparent papers with gloss and texture,  excellent for various  packaging applications.  This biodegradable material could prove to be the best alternative  to  the  millions of tons of nondegradable plastic garbage we keep  accumulating on a daily basis. 

These fibrils could also be excellent reinforcing materials.  Cellulose has an abundance of hydroxyl groups  which can form  extensive intra and inter chain  hydrogen bonding. Such  networks can  improve the mechanical properties of composites.  It has since  been established that  nano cellulosic fibrils perform far superior to conventional micro size  fibrous  reinforcements in composites. Japan's Ministry of Environments has already taken note of this and initiated Nano Cellulose Vehicle Project (NCV) to develop lightweight automotive components.  Calculations show that a 10% reduction in the weight of the vehicle  could  reduce fuel need by about  6%.  

Though cellulose is a plentiful, renewable resource,   challenges remain.  One that tops the list is the energy and cost intensive steps involved in the  isolation of cellulose  and its subsequent  processing  into  nano form. Global teams are at work to tackle this challenge.    Researchers at the  Edinburgh Napier University in collaboration with South African Paper and Pulp Industry (Sappi)  seem to have developed a  cost effective process  to turn wood pulp  into  "nanomaterial that could be used to build greener cars, thicken foods and even treat wounds".

REFERENCES:

1. "Developing fibrillated cellulose as a sustainable technological material. Li et    al.; Nature  590,pp 47-56, 4 February 2021

2. Tokyo Motor Show 2019: NCV (Nano Cellulose Vehicle Project)

3. Conversion Economics of Forest Biomaterials: Risk and Financial Analysis of CNC Manufacturing

4. A New Low-cost Process to Make Nano cellulose

4.American Process: Production of Low Cost Nanocellulose for Renewable, Advanced Materials     Applications.  

In the Sea, on the Land or Somewhere in between?

 Exactly 150 years ago on 1st February 1871, Charles Darwin wrote  to a colleague : 

"But if (and oh what a big if) we could conceive in some warm little pond with all sorts of ammonia and phosphoric salts,—light, heat, electricity &c. present, that a protein compound was chemically formed, ready to undergo still more complex changes, at the present day such matter wd be instantly devoured, or absorbed, which would not have been the case before living creatures were formed." 

Eighty years later in 1952 Stanley Miller and Harold Urey translated Darwin's thoughts into an experiment. Using water, methane,  ammonia, hydrogen and electric spark to mimic lightning, he synthesised amino acids, the building blocks of proteins. The hypothesis of oceanic primordial soup containing all possible chemicals  subjected to  Sun's ultraviolet rays and occasional lightning  giving rise to life's molecules gained  wider  acceptance.  

Miller-Urey  Experimental set up
Courtesy:wikipedia

But almost immediately  everything changed. The 1953 Nature paper by Watson and Crick established  deoxyribonucleic acid, DNA for  short,  as the macromolecule of life with the   genetic code   encrypted in a unique way in the DNA chain using 4 nucleobases: adenine, guanine, thymine and cytosine. In 2017, a group of scientists  repeated the Miller-Urey experiment  with suitable modifications and demonstrated that abiotic synthesis of nucleobases is also possible.  And then RNA replaced DNA as the original molecule!

The prebiotic soup model  has thermodynamic as well as kinetic   inconsistencies.  Issue is   not the formation of the building blocks, but the process of linking them and sustaining these linkages in a vast and seemingly limitless waterbody.  The  peptide bonds,  and the phosphodiester bonds, which form   the backbone of the proteins and  nucleic acids respectively,  are  both  extremely susceptible to water.  Biochemist Robert Shapiro  a vehement critic of the  primordial soup hypothesis  stated: "And of course the apparatus itself has no resemblance whatsoever to the primitive Earth. One of the popular magazines said that if this apparatus had been left on for a million years, something like the first living creature might have crawled out of it. And I say, if he'd left his apparatus on for a million years, he would have run up one hell of an electric bill " . 

Nonetheless the primordial soup model prevails, of course with modifications. For example  Professor John Sutherland  feels that small shallow ponds filled with  primordial soup,  and which have a tendency to dry out and refill might be a possibility.   The clay bed of such a pond  subjected to  periodic wet and dry cycles together with light and dark cycles of day and night would coax/catalyse  molecules to form, organise, hold together  and grow.  If the clay is rich in minerals such as quartz, then the issue of chirality could also be somewhat  settled. Because  as professors  Hazen and Sverjensky point out "such surfaces may have contributed centrally to the linked prebiotic problems of containment and organization by promoting the transition from a dilute prebiotic “soup” to highly ordered local domains of key biomolecules". 

Anthropogenic activities have irreversibly contaminated all possible terrestrial sites hence 

Professor Sutherland   is pinning  hopes on Perseverance, the rover  heading towards Mars.  Perseverance is programmed to land in the Jezero crater in Mars and collect and bring back  soil and rock samples. The assumption is that 3.5 billion years ago  this  crater could have been  a water body that underwent wet-dry cycles and  hence a faint probability that it could have supported life.  Scientists hope that Martian rocks and soil samples might hold secrets of  life,  that  the ancient biosignatures inscribed in there  might still be decipherable. 

Are we  going a bit too far ?

REFERENCES:

1. Life and Letters (Darwin 1887, Vol 3:168–169)

2. Miller SL (1953) A production of amino acids under possible primitive Earth conditions.           Science 117:528–529.

3. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions 

4. Formation of nucelobases in Miller-Urey reducing atmosphere.

5. A Simpler Origin for  Life   

6. Mineral surfaces, Geochemical complexities and the origins of Life

7. Chance, necessity and the origins of Life 

7. Perseverance Rover's landing site: Jezero Crater 

The Tall and Short of it.....

How tall can a plant grow? When will it flower?  How soon the fruits will ripen ?  Well  Gibberellins, the plant hormones   hold all the answers.   Adequate levels of gibberellin  in the system boosts  internodal elongation and plants   grow tall. Since all gibberellins are  diterpenoid acids, GA is the general abbreviation used for this class of hormones.    Deficiency   or total  absence of  GA renders the plants  short and stalky. In fact  GA ( or to be more precise its deficiency) revolutionised the  horticulture industry in the sixties. The rice semi-dwarf1 (sd1) and wheat Reduced height-1 (Rht-1) were the foot-soldiers  which successfully  ushered in the Green Revolution.  Initial studies indicated that a defect in one of the  GA genes, which adversely affected GA biosynthesis,  is responsible for dwarfism.

1. A plant lacking gibberellins  has an internode length of "0" as well as it is a dwarf plant. 

2.  A plant with a moderate amount of gibberellins and an average internode length. 

3. A plant with a large amount of gibberellins has a much longer internode length.

(Courtesy: wikipedia)

All gibberellins are diterpenoid acids

The life cycle of a rice plant, since germination goes through   3 stages:  the vegetative stage, the reproductive stage and the ripening stage.  It is during vegetative stage that GA builds up in the system and  internodal elongation begins. The plant grows in size,  sprouts leaves and ultimately  tillers (special grain bearing branches) develop. Focusing on two specific rice varieties,  the flood resistant deep water  tall variety C9285  and the shallow water  dwarf variety T65,  a group of Japanese scientists recently investigated how gibberellin  regulates stem growth and internodal elongation. 

Nagai et al studied the behaviour of both plants in shallow water (~5cm) as well as in deep water(~100cm) conditions.  Shallow or deep, internodal elongation was conspicuous in C9285 throughout  the vegetative stage, in conformity with ample concentrations of GA in the system.  However  in  T65 plants  endogenous gibberellin didn't appeared  during the stem growth phase but  only much later during the   transition from vegetative to reproductive stage. As a result  the plants got completely submerged in deep water during vegetative phase and got destroyed.  Even  with exogenous supply of  GA during vegetative phase T65 failed to elongate  while  C9285 exhibited the  added advantage.  

 

The fact that T65 didn't respond to  exogenous supply of GA, gave the indication that there are other factors  that work in concert with GA to promote/retard stem elongation.  Nagai et al  carried out  the DNA profiling of both plants. They located two genes in chromosomes 3 and 12 respectively of  C9285 which responded to the presence and level of GA antagonistically.   The  gene in chromosome 3 ,  was activated by GA and the protein it coded for   facilitated internodal elongation. This gene is aptly named Accelerator of  internode Elongation, ACE1 and the protein product as Accelerator.  The corresponding  ACE1 gene in T65 was found  mutated and nonfunctional.  And that explains why T65 didn't respond to exogenous GA.  However    the 68kb  gene  in chromosome 12 behaves differently.   Exogenous GA or deep water conditions  suppressed the activity of this gene in C9285 but not in T65 in either situation.  Follow up studies demonstrated that this gene codes for a protein that decelerates stem elongation. Nagai et al calls his gene DEC1, short for Decelerator of internode Elongation 1.   It could be  that the tug of war between  ACE1 and DEC1  is an evolutionary trait, a  survival tactic to facilitate the selection  of  shorter plants  in shallow waters  and taller  varieties in  deepwater  conditions.

Tailpiece:

The Dutch seem to be  the tallest people on Earth, according to a recent report,  with an average height of 182.5cm  for the male and 168.7cm for the female.  So is there a gene associated with height in humans?  It is accepted that genetic factors greatly influence height,  however  but multiple genes and their variants are implicated.  In addition nutritional and environmental factors also play very prominent roles. 

REFERENCES:

1. A Century of Gibberellin Research: 

2. Semidwarf (sd-1) "green revolution" rice contains a defective gibberellin  20-oxidase gene

Speilmeyer et al., Proc.Natl. Academy of Sciences 2002 99 (13) 9043-9048.

3. Antagonistic regulation of the gibberellic acid response during stem growth in rice 

Nagai et al Nature 2020 (584) pp109-114

4. Why are the Dutch  so tall?

5. Is height determined by genetics?