Kevin M. Esvelt | |
---|---|
Occupation | Assistant professor at the MIT Media Lab |
Academic background | |
Education | PhD in Biochemistry, Harvard University, B.A. in Chemistry and Biology, Harvey Mudd College |
Academic work | |
Discipline | Biology |
Main interests | |
Website | https://www.media.mit.edu/people/esvelt/overview/ |
Kevin Michael Esvelt is an American biologist. He is currently an assistant professor at the MIT Media Lab and leads the Sculpting Evolution group. [1] After receiving a B.A. in chemistry and biology from Harvey Mudd College, he completed his PhD work at Harvard University as a Hertz Fellow. [2] Esvelt developed phage assisted continuous evolution (PACE) [3] during his PhD as a graduate student in David R. Liu's laboratory. As a Wyss Technology Fellow, Esvelt was involved with the development of gene drive technology. [4] He focuses on the bioethics and biosafety of gene drives. [5] [6] [7] In 2016, Esvelt was named an Innovator Under 35 by MIT Technology Review . [8]
Esvelt was born to an elementary school teacher and a Bonneville Power Administration employee, and spent his childhood between Portland and Seattle. [9] Fascinated by biology from an early age, Esvelt first developed an interest in dinosaurs. [10] He discovered his passion lay in genetics after a trip to the Galápagos Islands, where he saw what evolution was capable of and wished to achieve similar results using science. [10]
Esvelt displayed a predilection for bold biological projects early on in his academic career. While an undergraduate at Harvey Mudd, he sought to reversibly induce male infertility using the sperm surface protein fertilin beta. [9] During this time, he was also an advocate for directed panspermia as a defense against extinction of all life, an idea he later rejected. [9]
While a graduate student in David Liu's laboratory, Esvelt demonstrated phage-assisted continuous evolution (PACE), a method of using bacteriophages to quickly and efficiently engineer proteins, promoters, and other biomolecules. [3] PACE has since been used to engineer proteases, [11] study antibodies in cancer research, [12] and understand the evolutionary dynamics of proteins. [13]
In 2013, Esvelt proposed the idea of using CRISPR in gene drives. [14] Although both methods had been in use independent of each other, Esvelt was the first to connect the two, and with colleagues show that CRISPR could make the implementation of gene drives easier and more efficient. [15]
The scientific - and ethical - implications of this new, more straightforward method of conducting gene drives were recognized almost immediately. One author compared gene drives to the fictional substance ice-nine, which freezes over any water it comes into contact with, propagating indefinitely as long as there is more accessible water to freeze. [16] While CRISPR-based gene drives have the potential to generate ecosystem alterations that benefit humanity (e.g., eliminating malaria by spreading infertility genes among a population of mosquitoes), unforeseen (or perhaps intentional) such modifications could result in irreparable environmental damage that directly or indirectly causes great harm to people and animals alike. [9] Keenly aware of the adverse effects even a well-intentioned and thought-out gene drive could have, Esvelt consults both scientists and the public in the course of his planning. [5]
In the wake of his controversial work on gene drive technology, and the failures of existing public health structures to adequately respond to the COVID-19 pandemic, Esvelt has become more active in biosecurity research. He argues that action must be taken soon, given that many researchers are able to construct or reconstruct deadly viruses in the lab, and there are few robust safeguards protecting humanity against accidental or deliberate release of these bioweapons. He envisions a three-tiered security system: early detection using a Nucleic Acid Observatory, [17] advanced preparation (involving stockpiling broad-spectrum medicines and better PPE), and better coordination between scientists, organizations, and countries. [18] Esvelt is also involved in SecureDNA, a technology to screen all synthetic DNA sequence orders to prevent actors from obtaining dangerous genes (e.g., from a deadly virus). [19]
To raise awareness about biosecurity issues and recruit interested scientists, Esvelt has made a number of appearances on-screen and in podcasts.
Esvelt appears in the Netflix series Unnatural Selection, where he discusses his efforts to conduct gene drives and the response of the local people who would be affected. [20]
He has also presented his biodefense program at a number of conferences.
Esvelt has appeared in several podcasts discussing biosecurity and his biodefense program.
Molecular biology is the study of chemical and physical structure of biological macromolecules. It is a branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions.
Viral evolution is a subfield of evolutionary biology and virology that is specifically concerned with the evolution of viruses. Viruses have short generation times, and many—in particular RNA viruses—have relatively high mutation rates. Although most viral mutations confer no benefit and often even prove deleterious to viruses, the rapid rate of viral mutation combined with natural selection allows viruses to quickly adapt to changes in their host environment. In addition, because viruses typically produce many copies in an infected host, mutated genes can be passed on to many offspring quickly. Although the chance of mutations and evolution can change depending on the type of virus, viruses overall have high chances for mutations.
In genetics, an insertion is the addition of one or more nucleotide base pairs into a DNA sequence. This can often happen in microsatellite regions due to the DNA polymerase slipping. Insertions can be anywhere in size from one base pair incorrectly inserted into a DNA sequence to a section of one chromosome inserted into another. The mechanism of the smallest single base insertion mutations is believed to be through base-pair separation between the template and primer strands followed by non-neighbor base stacking, which can occur locally within the DNA polymerase active site. On a chromosome level, an insertion refers to the insertion of a larger sequence into a chromosome. This can happen due to unequal crossover during meiosis.
M13 is one of the Ff phages, a member of the family filamentous bacteriophage (inovirus). Ff phages are composed of circular single-stranded DNA (ssDNA), which in the case of the m13 phage is 6407 nucleotides long and is encapsulated in approximately 2700 copies of the major coat protein p8, and capped with about 5 copies each of four different minor coat proteins. The minor coat protein p3 attaches to the receptor at the tip of the F pilus of the host Escherichia coli. The life cycle is relatively short, with the early phage progeny exiting the cell ten minutes after infection. Ff phages are chronic phage, releasing their progeny without killing the host cells. The infection causes turbid plaques in E. coli lawns, of intermediate opacity in comparison to regular lysis plaques. However, a decrease in the rate of cell growth is seen in the infected cells. M13 plasmids are used for many recombinant DNA processes, and the virus has also been used for phage display, directed evolution, nanostructures and nanotechnology applications.
CRISPR is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes and provide a form of acquired immunity. CRISPR is found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea.
A guide RNA (gRNA) is a piece of RNA that functions as a guide for RNA- or DNA-targeting enzymes, with which it forms complexes. Very often these enzymes will delete, insert or otherwise alter the targeted RNA or DNA. They occur naturally, serving important functions, but can also be designed to be used for targeted editing, such as with CRISPR-Cas9 and CRISPR-Cas12.
Daisy chaining DNA is a form of gene editing, or "gene drive", which, unlike CRISPR, is self limiting. This means that any alteration made in the laboratory to a gene sequence is limited to a local population only, and cannot be passed on to global populations. It occurs when DNA undergoing PCR amplification forms tangles that resemble a 'daisy chain.' In essence it teaches DNA to count, so that the new strain will only reproduce for a fixed number of generations. It may be useful for instance to alter a particular strain of wheat to suit a local area with no danger of the new strain escaping into wild populations. As a new technique, it must be studied under carefully controlled conditions until it is better understood. Research is typically performed in closed systems on organisms such as yeast, fruit flies, mosquitos, and rapidly evolving nematode worms.
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases, and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).
Cas9 is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna.
David Ruchien Liu is an American molecular biologist and chemist. He is the Richard Merkin Professor, Director of the Merkin Institute of Transformative Technologies in Healthcare, and Vice-Chair of the Faculty at the Broad Institute of Harvard and MIT; Thomas Dudley Cabot Professor of the Natural Sciences and Professor of Chemistry and Chemical Biology at Harvard University; and Howard Hughes Medical Institute Investigator.
A gene drive is a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring. Gene drives can arise through a variety of mechanisms. They have been proposed to provide an effective means of genetically modifying specific populations and entire species.
Cas12a is a subtype of Cas12 proteins and an RNA-guided endonuclease that forms part of the CRISPR system in some bacteria and archaea. It originates as part of a bacterial immune mechanism, where it serves to destroy the genetic material of viruses and thus protect the cell and colony from viral infection. Cas12a and other CRISPR associated endonucleases use an RNA to target nucleic acid in a specific and programmable matter. In the organisms from which it originates, this guide RNA is a copy of a piece of foreign nucleic acid that previously infected the cell.
Biotechnology risk is a form of existential risk from biological sources, such as genetically engineered biological agents. The release of such high-consequence pathogens could be
CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.
Anti-CRISPR is a group of proteins found in phages, that inhibit the normal activity of CRISPR-Cas, the immune system of certain bacteria. CRISPR consists of genomic sequences that can be found in prokaryotic organisms, that come from bacteriophages that infected the bacteria beforehand, and are used to defend the cell from further viral attacks. Anti-CRISPR results from an evolutionary process occurred in phages in order to avoid having their genomes destroyed by the prokaryotic cells that they will infect.
Prime editing is a 'search-and-replace' genome editing technology in molecular biology by which the genome of living organisms may be modified. The technology directly writes new genetic information into a targeted DNA site. It uses a fusion protein, consisting of a catalytically impaired Cas9 endonuclease fused to an engineered reverse transcriptase enzyme, and a prime editing guide RNA (pegRNA), capable of identifying the target site and providing the new genetic information to replace the target DNA nucleotides. It mediates targeted insertions, deletions, and base-to-base conversions without the need for double strand breaks (DSBs) or donor DNA templates.
Phage-assisted continuous evolution (PACE) is a phage-based technique for the automated directed evolution of proteins. It relies on relating the desired activity of a target protein with the fitness of an infectious bacteriophage which carries the protein's corresponding gene. Proteins with greater desired activity hence confer greater infectivity to their carrier phage. More infectious phage propagate more effectively, selecting for advantageous mutations. Genetic variation is generated using error-prone polymerases on the phage vectors, and over time the protein accumulates beneficial mutations. This technique is notable for performing hundreds of rounds of selection with minimal human intervention.
The eradication or abolition of suffering is the concept of using biotechnology to create a permanent absence of involuntary pain and suffering in all sentient beings.
Diversity-generating retroelements (DGRs) are a family of retroelements that were first found in Bordetella phage (BPP-1), and since been found in bacteria, Archaea, Archaean viruses, temperate phages, and lytic phages. DGRs benefit their host by mutating particular regions of specific target proteins, for instance, phage tail fiber in BPP-1, lipoprotein in legionella pneumophila, and TvpA in Treponema denticola . An error-prone reverse transcriptase is responsible for generating these hypervariable regions in target proteins. In mutagenic retrohoming, a mutagenized cDNA is reverse transcribed from a template region (TR), and is replaced with a segment similar to the template region called variable region (VR). Accessory variability determinant (Avd) protein is another component of DGRs, and its complex formation with the error-prone RT is of importance to mutagenic rehoming.
Make People Better is a 2022 documentary film about the use of genetic engineering to enhance two twins girls to be immune to HIV. Directed by Cody Sheehy of Rhumbline Media, it was originated by Samira Kiani, a biotechnologist then at Arizona State University. It focusses the circumstances involving Chinese biologists He Jiankui who created the first genetically modified humans in 2018. Featured experts included Antonio Regalado, senior editor for biomedicine of MIT Technology Review, who first discovered and revealed the secret experiment, and Benjamin Hurlbut, a bioethicist at the Arizona State University.