4 clarifications about the history of the universe

James Peebles

Certain statements by James Peebles, recent Nobel Prize in physics, have aroused controversy, although what he said is not something new, as theoretical physicists have long been saying precisely the same thing.

The Big Bang theory was proposed in 1931 by Georges Lemaître, by extending to the past the Hubble-Lemaître law. In 1948, Ralph Alpher and Robert Herman predicted that, if the Big Bang theory is correct, there must be a cosmic background radiation with a temperature close to 5 Kelvin. In 1965 Arno Penzias and Robert Wilson discovered the existence of such cosmic radiation, whose temperature proved to be 2.72548 Kelvin. The temperature is exactly the same in all directions, except for two effects that cause small differences, but never affecting more than the third decimal place.

Synthetic life, is it possible?

Frankenstein's monster

In the previous two posts in this series we have seen that the generation of synthetic life in the laboratory is probably a process more difficult than some optimists imagine.

Let’s look at one of the latest experiments in synthetic biology: George Church and Nili Ostrov, Harvard biologists, are trying to build a strain of the bacterium Escherichia coli immune to all existing viruses. How? By changing its genetic code so that viruses do not understand it and cannot use the bacterial cellular machinery to reproduce. Since the genetic code is redundant, it is possible to replace one of the codons encoding the amino acid arginine (AGA) with another that also encodes the same amino acid (CGC), and all the genes of the bacterium would go on generating the same proteins. This would be done with several rare codons. But since viruses would continue to use the substituted codons, the bacterial cell machinery would no longer be able to understand the DNA of the virus. This part of the job is almost finished. When it is done, it would also be necessary to eliminate the transfer RNAs of the missing codons and ensure that they are not remanufactured, so that the cellular machinery can no longer use them.

Note that the work done so far is the manipulation of the data recorded in the DNA. It is equivalent to changing the information contained in the hard disk of a computer so that it stops using a certain instruction of the language of the machine, by replacing it with another equivalent instruction. We are still very far from synthetic biology in the strict sense. Will it be possible to synthesize life in the near future?

Synthetic life, near or far?

In the previous post I detailed some recent advances in the field of synthetic biology, and asserted, without saying why, that I don’t think the goal of creating an artificial living cell is as near as some optimistic researchers believe, such as Craig Venter.

To explain why, I’ll make a comparison between a living cell and one of our most complex artifacts: the computer. A computer consists of the following two main parts:

1. CPU (central processing unit): as its name indicates, it’s the control center and the place where programs are executed. One of its fundamental elements is the machine language, a relatively complex binary code that the circuits of the unit interpret and execute. Every program, in order to run, must be written in machine language.
2. Memory. There are several types: hard disk, which stores the programs and data accessed by the computer, including the operating system, although many of them will never be used; cache memory, faster than the hard disk, which stores those programs and data currently being used, to speed up their process; external memories (such as flash memory), used to transmit data and programs from one computer to another, or to save copies in case of loss of information.

Synthetic life, when?

Craig Venter

First, a clarification. We must distinguish two very different fields of research:

1. Artificial life: this is the part of computer engineering that tries to build programs that emulate the behavior of living beings: either artificial living beings, or colonies of living beings, such as anthill or hives.
2. Synthetic life: this is the part of biology that tries to build artificial living cells from simple chemical substances. So far, this goal has not been achieved.

Shall we be able one day to make life in the laboratory? A few important steps have been taken during the last half century.

• In 1967, Arthur Kornberg (1959 Nobel Prize together with Severo Ochoa) used the enzymes DNA polymerase (discovered by him) and DNA ligase to duplicate the DNA of the fX174 virus, which is made of 5386 nucleotides, and showed that the copy of the virus could infect bacteria, as the original virus. For those who argue that viruses are alive, this was the first generation of artificial life, but the authors of the experiment, who did not share that opinion, insisted before the press that their discovery shouldn’t be presented in that way.
• In 1976, Frederick Sanger (the only winner so far of two Nobel Prizes in chemistry, in 1958 and 1980) managed to sequence the genome of the fX174 virus, i.e. obtain the complete ordered list of its nucleotides. This was the first genome successfully sequenced.
• After his spectacular triumph in the Human Genome project, when a small private company achieved results comparable to the multi-million dollar project sponsored by the United States Government, biologist Craig Venter dedicated his efforts to synthetic biology. The first thing he did was build artificially DNA molecules, starting from the list of their nucleotides, and make those molecules act inside living cells as their natural models do. In 2003, Venter and his team built the first “artificial DNA” by generating the DNA of virus fX174, using DNA synthesizer machines, and starting from the list of the virus nucleotides obtained by Sanger. This was not the first artificially constructed virus, since in 2002 Eckard Wimmer and his team had managed to synthesize RNA from the poliovirus that causes polio, starting from its genome (the list of its nucleotides).

• After this achievement, Venter and his team moved to more complex organisms, about which there is no doubt that they are living beings, and to begin with they chose the group of living cells with the smallest known genomes: mycoplasmas, very small bacteria without a hard membrane, which makes their handling easier. The smallest genome belongs to Mycoplasma genitalium and contains 582,970 nucleotides and 480 genes. This genome was sequenced by Venter and his team in 1995, and in 2007 they managed to synthesize it (with some changes, to facilitate its identification) from the list of its nucleotides.
• The next step, completed in 2007, was transplanting the DNA from a bacterium into another bacterium of a related although different species, to see if it could be expressed there. For this they chose two similar species: Mycoplasma capricolum and Mycoplasma mycoides, which have a larger genome with 1,010,023 and 1,083,241 nucleotides respectively, 91.5% of which are the same, which made it likely that the genome of one species would work in a cell of the other. They extracted the chromosome from M. mycoides, inserted it into M. capricolum cells and allowed the cells to reproduce, hoping that some of the daughter cells would be left only with the transplanted genome, as it happened. The DNA taken from M. mycoides was able to reproduce correctly in a cell of M. capricolum, so this cell had changed species.
• Successive research, which ended in 2010, was aimed at artificially synthesizing DNA from M. mycoides and inserting it into cells of M. capricolum, to see if the change of species could be made, not from the DNA of a living cell, but with an artificially generated copy. This experiment also ended successfully.

Venter himself acknowledges that his experiments have not resulted in the synthesis of living cells. In every case, they have started from pre-existing cells whose DNA has been replaced by another DNA, either from a different cell, or artificially generated. To be able to say that life has been manufactured, it would be necessary to design synthetic DNA and introduce it into an artificial membrane, with artificial contents, getting the artificial cell to reproduce. Until this is achieved, the synthesis of life in the laboratory won’t have happened. Although Venter does not risk predicting a date when this will have been achieved, he doesn’t think the goal is too far away.

I think he’s wrong. Perhaps we shouldn't be too optimistic. Remember the horizon effect. In the next post I’ll explain why.

The same post in Spanish
Thematic Thread on Synthetic and Artificial Life: Previous Next

Manuel Alfonseca